Grand Unifying Guesses/Mass Effect

Shepard's death is a cover story.

 * He actually spent most of those two years reading TV Tropes. But by the time of the game, TV Tropes has evolved into a predatory AI Hive Mind, and the Lazarus project was an effort to free the Commander from the Virus. The collector attack was his brain using tropes to react to the traumatic experience of being pluged out of the Troper Matrix, who wanted to hardwire the Evil Overlord List into the Shepard's brain, and conquer the galaxy through him.

The Hanar were once members of TV Tropes.

 * They shed off all organs they did not need to browse TV Tropes, therefore becoming flying jellyfish with many arms for opening new tabs. They were never able to fully kick their habit of referring to themselves as This Troper.

The Reapers are from a galaxy far, far away.

 * The Reapers are, as established in-game, synthetic beings that hide in between galaxies until their Phlebotinum opens a doorway to their hiding spot, signaling them to destroy all organic life in the Milky Way before returning to hiding and repeating the cycle, perpetuated many times over countless millenia. Obviously, they were created by the Rakatans with the Star Forge. The Star Forge was not the ultimate achievement of the Infinite Empire, it was merely the next step in their technology, and the Reapers were another step; sentient machines. When the Rakatans started dying out, they hoped the Reapers might be their salvation; sentient machines capable of FTL, whereas their standard ships relied on the crew having a connection to the Force, a connection the entire species was losing. But the Reapers, being created from the Star Forge, a thing of the Dark Side, find the Force maddening. Maybe they hate it on a moral level, maybe it gives them a migraine. So they abandoned the Rakatans and left, making their own technology (Mass Relays) to leave that galaxy far, far away. Somewhere near the rim, there must be a huge Mass Relay identical to the Citadel in the Milky Way, but unpopulated; its only purpose was to get the Reapers out of that galaxy. For some reason, they fled to the Milky Way. They either thought it was devoid of life, or it had so little life that the Force was a non-issue, and they could exist in comfort. Life in the Milky Way started to develop, until it maddened them to the point of killing it all. But they can never do a complete job; the galaxy is a large place, so they wait for life to develop along their preset rules before destroying it again, hoping that eventually, they'll do a thorough enough job for it to never come back. This would not even be remotely possible in their home galaxy, where there is simply too much life to wage a successful war against.
 * As a corollary, the true enemy alluded to in KotOR 2 are the Reapers. No one knows where Revan is because he found the original  and accidentally sent himself to the Milky Way.
 * But we don't know how long ago Star Wars is, for all we know he may have been killed with the Protheans... or earlier.
 * This opens up the possibility that the biotics are actually twisting the Milky Way's own Force, but they have a more scientific sort of understanding of it than the Jedi and Sith do. For that matter, the primary asari religious concept that "all life is connected" sounds a lot like the Force anyway.
 * As a second thought, the Reapers don't hate the Force, they use it as fuel. That's how they indoctrinate people, they suck away the force to power themselves until the victim is lacking the fundamental element of life that makes them sentient, thus the lack of will and need of Sovereign's guidance. That's also why they "reap" the galaxy every 50,000 years; even in standby mode they still have to recharge once in a while and, with their massive numbers, they have to go on a campaign of xenocide just to fill up.
 * I wrote the original WMG and actually like this better. Also, it opens up an interesting parallel with the way the Force is treated in KotOR (see Darth Nihilus and, for that matter, fanon for the Exile being darksided.)
 * After ME2,.

On a related note, Mass Effect is the ancient history of the Star Wars Galaxy

 * We know from the descriptions of Xim the Despot's Empire that accelerated projectile weapons like those used by the species of Mass Effect were the main armaments used before the rise of the Galactic Republic. When the Reapers finally return, humans succeed in destroying them by converting the Citadel into a massive element-zero powered sun-destroying tractor beam, i.e. Centerpoint Station. But they are nearly wiped out in the process - only the remote and sparsely populated colony worlds of Coruscant and Corellia avoid being destroyed or indoctrinated. The Citadel Council races of Mass Effect's time period become legends known only as "The Celestials." The asari, due to their practice of mating with other species, undergo mutation that makes them a bi-gendered race which results in the birth of the Twi'lek species. The hanar become the Gree and, wanting to hold on to the sacred relics of the Prothean "Enkindlers," are the only species which successfully preserve a series of mass effect relays, which become known as "hypergates" but will sadly be only non-operational relics that no one knows how to use by the time of the Empire. The drell become the Barabels, the turians become the Taung/Mandalorians, the salarians become the Duros, the keepers become the Verpine and Killiks, and the geth become the first droids.
 * Wouldn't it make more sense if Star Wars was Mass Effect's history?
 * Seeing how Mass Effect is basically Knights of the Old Republic with the setting cleaned up to remove the worst excesses of Star Wars, and that game was concerned heavily with the origin of the earliest known history of the Star Wars galaxy, this one is more insightful than your average WMG.

The Illusive Man is G0-T0.
Tying into both "the Reapers are from Star Wars" and "the Ilusive Man is an AI." Obviously, G0-T0 didn't die on  Instead, he survived and, believing the Republic to be ultimetly unsalvagable, set off to another galaxy—ours. His primary programming is still to try and save "galactic civilization," and seeing in the Council the same problems as the Repbulic, decides to set up a dictatorship. The only species he remembers from a galaxy far, far away is humanity, so he takes over Cerberus (from the inside, natch)) and begins to angle for human supremecy.

Shepard will eventually become Minsc in Baldur's Gate.

 * After repeated exposure to Reapers and mild indoctrination waves, it's not too big a stretch for Shepard's mind to become affected. This would eventually result in him forgetting his name and much of his skills and running away with his pet space hamster, which he renames (or named) Boo. Somehow he found his way into the forgotten realms, and eventually joining the party.

Mass Effect takes place in Warhammer 40000 during the Dark Age of Technology

 * Strange, ancient alien ruins on Mars home to incredibly advanced alien technology? Check. Incomprehensibly ancient and evil sentient machines bent on eradicating life? Check. Psychic powers shown to have debilitating effects on their users? Check. Golden age of humanity exploring the galaxy on even terms with xenos? Check. Monogender bruiser race with fighting hardwired into their brains? Check. Psychic "seer" race with much potential for Squick? Check. Humans Are the Real Monsters and Humanity Is Superior in the same setting-sometimes in the same people? Check. Really nasty ammunition for the big guns? Check. Outrageously huge and appropriately armed space battleships? Check. Powered armor employed by everyone? Check. Religious fanatics in space? Check. Mysterious precursors who left lots of abandoned technology and may have left lots of abandoned races littering the galaxy? Check. Mysterious element vital to society that no one has any clue how it works? Check (think Warp here). Inertialess drive equivalent, due to an ancient and evil race? Check. The galaxy is doomed? Probably...
 * So, who's the God Emperor of Mankind? Also, if you go Paragon and make everybody best buddies, do you prevent 40k style disaster?
 * Admiral Hackett is the Emperor. You know, the vaguely Mediterranean sounding guy who manipulates everybody but never does something himself because is busy building the Primarchs. Also, Paragon Shepard will be an ultrasmurf Ultramarine and renegade Shepard will be an Iron Warrior in the future.
 * The troper above may be correct with Admiral Hackett being the God-Emperor, but wrong on Shepard - Renegade Shepard is a psyker and will become Malcador the Sigilite, the Emperor's right-hand-man. Paragon Shepard will die somewhere, unmourned and remembered only because he lacked the courage to do what needed to be done for humanity's survival.
 * Would this make the Reapers the Necrons/C'tan?
 * Also, Tuchanka is eventually renamed Catachan.
 * Wait, "monogendered bruiser race with fighting hardwired into their brains"? Who, the krogan? They have females. The asari? They're not (all) bruisers and definitely don't have "fighting hardwired into their brains". The turians? They also have females. Salarians? Definitely not bruisers. The vorcha? Well, actually, considering how adaptive the vorcha are...
 * Also, "outrageously huge ... space battleships"? A dreadnought measures at most one kilometre in length, according to the in-game Codex. Battleships of the Imperial Navy are eight times that in length.
 * Well they do have 38000 years and the Reapers for inspiration.
 * Post-Mass Effect 3: Theory is true

The Protheans Are Really Brainboyz!

 * They created the Orks as a weapon against the Reapers and these Orks are chilling on some planet just fucking shit up in normal Orky style. How did they survive you ask? Have you tried to eradicate an Ork infestation? That's what I thought. You can't! Sure the Reapers killed them all but since when has that stopped a good Ork Waaagh!!? The Reapers eventually said screw it and left them alone since they couldn't kill them off since they just sprung back more numerous than before a few weeks later. Shepard will eventually discover these Orks and let them off said planet and point them towards the Reapers and hope for the best. Sure the Council will be pissed but they fail to realize who they're dealing with. They're dealing with Commander "Fucking" Shepard. And Shepard does whatever Shepard wants whenever Shepard wants.

The Reapers are really Necrons.

 * Let's face it they show up every 50,000 years to go on a killing spree. Planets get scourged, people die, massacres start piling up, you know, quality Necron-style entertainment. And when they are done? They go back to sleep somewhere and wait for a new group of victims to present themselves. Why do they do this? The C'Tan are sleeping somewhere even more remote and make the Reapers look like domesticated house cats. Why aren't we totally screwed? Fortunately, the C'Tan are EXTREMELY lazy and would rather have their household pets do the killing for them. What happens when the Reapers die? Well, they get really pissed, not the "Aw, shit! It's those fucking kids again!" pissed. But the "Ok, that does it! There goes the universe!" pissed. It's time for a Roaring Rampage of Revenge with an Earthshattering Kaboom on a galactic scale. You know Apocalypse How? That page doesn't even have a category to describe how bad the C'Tan will fuck up the universe. At least until the Normandy shows up to do that thing it does whenever it stumbles across C'Thulhu. And that'll be that, C'Tan dead. And Joker will walk off with every single woman in the universe because he was just faking Vrolik's Disease so that no one would figure out he's the biggest Badass the universe has ever known. Why do you ask? BECAUSE HE'S FUCKING JOKER! THAT'S WHY!
 * Perhaps they're not Necrons, but servants of another C'Tan Star God.
 * And the answer is: [[spoiler:Jossed, since the Reapers' creator is motivated out of a twisted sense of altruism. Something the C'Tan aren't capable of.[/spoiler]

Xenogears is set in the future of the Mass Effect universe

 * The Reapers manage to successfully invade the galaxy circa 2510 AD. Almost all sentient life in the galaxy is wiped out, but some humans from Earth manage to evacuate the galaxy, eventually arriving at a planet they name "Neo Jerusalem." Knowing that they will have to face the reapers sooner or later, these humans develop a superweapon known as Deus. As AI is always a crapshoot, Deus goes rampant, first on the planet Miktam 04 Beta, and then while it is under transport close to the Xenogears planet, where it crashes. The bad news of all this is that Deus is essentially turned into a Reaper. The good news is that Fei destroys it. The bad news then is that humanity is left defenseless against the Reapers. The good news is that Fei is a cosmic horror killer, and humanity will survive.
 * Revelations in Mass Effect 2 lend more supporting evidence.
 * Damn.

Likewise, Chrono Trigger and Chrono Cross also take place somewhere in the Mass Effect universe

 * During one of the Reaper's extinction cycles, one Reaper crash-lands on a planet suspiciously similar to Earth. As it fell, it's element zero core disintegrated and scattered itself all across the planet's surface. For some reason, this eezo becomes a super-concentrated red "isotope" that has the ability to warp time as well as space. Unable to leave the planet's surface, the crashed Reaper (which we all know as Lavos) began instead to manipulate life on the planet so it could be used to produce new Reapers, which is exactly what happens during Chrono Trigger. Magic? Super-advanced biotics due to the presence of dreamstone instead of normal element zero. Queen Zeal ? Indoctrinated. The Lavos Core? Duh, it's Lavos' equivalent to . The mutants in 2300AD and on the Black Omen? Husks. Really, the only thing that would come purely from Mass Effect is Lavos' origin; everything else is backed up by speculation in Trigger and Cross.
 * That would explain why there is a "Choras" in both.

Mass Effect takes place in an alternate Halo universe
The volus are the grunts, who use a deeper setting for their vocodors, and the Protheans are the same speceis that preceded the Forerunner, who never made it off of Earth. The Flood evolved slightly differently, focussing on consuming plants and became the Thorian; sinister, but not galaxy consuming. The other aliens from the Halo verse either didn't recover from the last Reaper incursion, or since there was less tech scattered willy-nilly on inhabited planets, they haven't joined the galactic community on their own.
 * The other races, like the Flood, evolved differently, Brutes evolved into krogans, Elites evolved into turians, Hunters evolved into elcor, etc.

Mass Effect is set in the future of the Cthulhu Mythos

 * Cthulhu/Starspawn of Cthulhu: The standard squiddy Reapers.
 * Nyarlathotep the crawling chaos:
 * Shoggoths: the geth.
 * Mi-Go: Collectors.
 * Hastur the god of shepherds: ?!?
 * I actually equated Sovereign to Atlach-Natcha (Spidery thing that opens the gate for all the other Mythos Gods to come through), the Disabled Reaper to Cthulhu (They even CALL it a sleeping god), and Harbinger to Hastur (Big on possession, Those he dominates turn yellow.)
 * Personally, I'd vote the Illusive man as Nyarly.
 * If TIM is Nyarlathotep, one has to question, who is Yog-Sothtoth...

The Protheans are the star-spawn of Cthulhu, or Cthulhi.

 * You know those guys with tentacles in their faces, like the prothean statues? Lovecraft was right, sort of: the eldritch horrors are just really advanced aliens.

The Combine from the Half Life universe fled the Reapers.

 * The whole reason they became a pandimensional empire in the first place was that they were using their tunnelling technology to escape the Reapers. In the Mass Effect universe, they left what we'd consider to be the "prime" dimension and never returned. In the Half Life universe, the Black Mesa incident caused them to take an interest in mankind prior to their contact with the Citadel races. The apparent telekinetic ability of Advisors? Biotics. Their telepathy? An adaptation of the tech behind Reaper indoctrination, something else powered by their amps. Overwatch pulse rifles use identical tech to the hand-sized mass accelerator rifles of Mass Effect, and Strider distortion cannons are directly analogous to the unstable mass effect fields created by disruptor weapons.
 * Also raises the troubling issue that Breen was right, and there really are worse things out there than the Combine!
 * Which could mean that G-man serves a higher power than even the Combine. I mean, come on now, we all know he's a big player in Mass Effect. Yeah, you know who I'm talking about.

Dragon Age is a distant prequel to Mass Effect.

 * When you hack open the first lock on Eden Prime, the first thing the archaeologist inside says is "Humans! Thank the Maker!" The subtitles even go out of their way to capitalize "Maker". Ashley asks if you have a problem with her belief in God, which implies that Christianity is not as predominant amoung humanity, but it's not because we've Outgrown Such Silly Superstitions; it's because the leading religion on Earth is the Cult of Andraste, and Christianity is a niche belief. Dragon Age's magic is biotics shrouded in mysticism: the science of the time is unaware of element zero. Lyrium acts as a biotic catalyst, and eventually becomes one of the main components in biotic implants, dropping the need for lyrium staves and potions. Dragon Age's health potions are a crude form of medigel. Humankind brought elves all the way to extinction, and the isolationist dwarves holed up underground for long enough that they've become forgotten history, leaving the human-exclusive Earth the only face the rest of the galaxy sees.
 * The Maker may refer to a non-human religion; faiths seem to intermingle in the Mass Effect universe. Some turians, for example, embrace Buddhism, and the hanar religion worshipping the Enkindlers is popular among young drell.

SHODAN from System Shock is based on Reaper technology.
Citadel Station, anyone?

The Reapers are anti-spirals.

 * The Reapers were originally an organic race who realized that their evolution would eventually doom the universe. In an effort to maintain the existence of the universe, they became deathless machines, stopping their own evolution, and decided to periodically wipe out civilization in the universe. The Reapers don't actually enter a dormant phase, they just travel between 10-20 differnet galaxies, wiping out civilization in one before moving on to the next. They leave mass effect technology so other civilizations depend on mass effect technology instead of using spiral energy.

The Reapers are really the Ur-Quan wearing power suits.

 * Think about it: The creepy monotone that sounds vaguely threatening, all those "eyes" and "arms," the same sort of evil schemes...

The Reapers are the offspring of Skynet.

 * And Mass Effect is really set in the Terminator universe. John Connor defeats the machines, but Skynet manages to send out a space probe billions of years into the past. It founds a new machine civilization, which becomes the Reapers we know today. Centuries later for humanity and eons later for the machines, the second great machine war will start anew.

The Illusive Man is a Narutard.

 * He has blue-on-black cybernetic sharingan. Clearly someone is reading too much of a certain 180 year old manga. As a corollary, given his resources, it probably works. At some point in Mass Effect 3, he will be forced into combat and reveal his ability to fire superpowered lasers out of one eye, hypnotize enemies with the other, and,

Battlestar Galactica and Mass Effect take place in the same universe--same galaxy, even.
Fifty thousand years and change ago, not long before their extinction, Prothean scientists took a few small groups of Homo sapiens from Earth to twelve outlying Prothean colonies to study their evolution. Unfortunately, the scientists were abruptly drafted and called away when the Reapers attacked, leaving human society to develop on its own, much as it did on Earth. Hence, you have the 12 colonies. The Lords of Kobol are the Protheans, or at least the primitive human interpretation of them.

Meanwhile, it's not too ridiculous to assume that, much like the geth, the Cylons encountered Sovereign at some point—hence, the monotheistic Cylon religion.

As for why the Colonies haven't run into the asari, turians, or even the Alliance... perhaps the mass relays for the Colonies were destroyed, and they've had to rely on standard FTL to get everywhere. Boy, the Colonial fleet is in for a surprise when they finally get to Earth...
 * The Colonial Fleet has encountered the other races, but by the time they did, they'd become so adapted to the sterilized atmospheres of their ships that they couldn't survive in a normal atmosphere without spacesuits. The Alliance would never believe the quarians were human. It also follows logically that the Geth are just more advanced models of Cylon.
 * One big problem with that; the quarians are dextro-amino acid based. The Colonials, being human, would be levo-amino acid based. And even if the biochemistry wasn't an issue, the quarians physically differ from humans in quite a few areas (three fingered hands, differently shaped legs, etc).
 * Alternatively, when the RTF gets to Council space, they and the quarians are going to get on like a house on fire, if only because it's hard to think of two races from diffent series who have more in common (both created A Is, both had said A Is turn on them, both lost their homeworld(s), both have been wandering around in a run down migrant fleet ever since, both have had really crap luck). On the other hand, things might get difficult for the RTF if/when the Council finds out why they're an RTF.

Shepard is Revan.
After Revan went to the Outer Rim, Revan found a way to our Galaxy, got another mind wipe and is now known as Shepard.

The Reapers are The Great Beings.
After they lost their planet, the Great Beings left the solar system and proceeded into dark space. By the time they found a galaxy capable of supporting life, they were on the verge of death. They harvested that galaxy's residents, turning their biomatter into a substance comparable to Protodermis they could subsist on. They left some species alive and used their experience in creating biomechanical entities to shape the flow of technology for the remaining species, ensuring that there would be sufficient technological and biological matter to harvest.

In spite of being starved, they still have the urge to create. They use some of the harvested material to create beings such as the Human-Reaper.

Y'knew It Was Comin': The Catalyst is an Angel.
Iruel, to be precise.

In this universe, the seeding of life by the builders of the White and Black Moons went as planned due to a different, much, much earlier schedule (a few eons, to be precise). Lilith's children proved to be much more successful, provoking the builders to spread her Fruit of Wisdom across the galaxy, hence why so many races are so humanlike. Adam's children were also successful, but Iruel's machine race was distrusted by the other Angelic life forms, resulting in a war of extinction that nearly destroyed the galaxy, hence why the builders went with the Lilim instead for the predominant ethos of the galaxy (at least a Proud Warrior Race doesn't damage the fabric of reality when they fight..). Iruel survived however, feeling embittered by abandonment and the war that destroyed his descendants.

When it became clear that the machine races the Lilim built inevitably succumbed to distrust and war, Iruel snapped at what he saw as the mistakes of Adam's children being repeated in the favored children of the builders, and decided that not only would he put an end to what he had come to see as an inevitable result of sapience, he would use the souls of the Lilim to rebuild his own race-what would become the Reapers. The sludge the components of Reapers are processed into is, obviously, LIV, and the Human-Reaper and presumably it's cousins are Angel Cores created from the LIV in imitation of Iruel's own.

Of course, there was a slight problem with this-namely, the Fruit of Knowledge and the Fruit of Life were never supposed to mix, thus the Reapers were driven Ax Crazy by the Lilim's wisdom and Iruel's powers conflicting. Thus, by the time Shepard shows up, Iruel has realized what a terrible mistake he's made, and submits to judgement for his actions. Should you go Synthesis however, he gets a small concession-with Shepard already being a fusion of mechanical and organic life, his/her AT Field provides a basis for a much more natural fusion of Iruel's race and the Lilim, resulting in an entirely new form of life that embodies balance between Adam and Lilith, greater than the sum of it's parts.