Apocalypse How/Class X-3

Galactic-scale Physical Annihilation. Via some means, billions of stars, nebulae, pulsars, and so forth, along with the super-massive galactic-core black hole(s) at its center are destroyed. Utterly.

Multiple Media

 * The Hitchhiker's Guide to the Galaxy saga makes brief reference to a planet's residents killed in galactic snooker. The result of an entire game can only be imagined.

Anime and Manga

 * Majin Buu's rampage in Dragon Ball millions of years ago, though it could easily reach X-4 if he was left unchecked.
 * Going further, Vegito averted the destruction of the barriers between dimensions, which presumably would have destroyed all reality.
 * In the movies, Broly destroyed much of the South Galaxy.
 * Gunbuster: Humans turned the planet Jupiter into a bomb capable of blowing the core right out of the Galaxy, in order to wipe out a race of space monsters, who themselves destroyed stars simply through their reproductive process.
 * In Tenchi Muyo!, the Milky Way is almost destroyed by two choushin struggling. The multiverse was about to be destroyed by Tenchi's leaking power. Note that about 1/4 of the Milky Way got obliterated simply from one choushin blocking another's punch. It's hinted they could end the universe on a whim if they really wanted to. And Tenchi can go beyond that and, in theory, kill the choushin.
 * Strongly implied as a possibility in Sailor Moon Stars (manga) both by Galaxia and Sailor Cosmos, the latter of who utilized all the Sailor Senshi Crystals in the Galaxy to create the Cosmos Crystal, and soon after destroyed the Galaxy Cauldron.

Comicbooks

 * Galactus from the Marvel Universe has this as his MO. He eats populated worlds.
 * Forget Galactus, he was upstaged by Thanos, a guy who seems to have no motivation other than wanting to exterminate all life in the universe. When Galactus got in this guy's way, Thanos more or less pimp slapped him to oblivion. Keep in mind, this was BEFORE he had the Infinity Gauntlet, which then allowed him to essentially "think" parts of the universe away.
 * If you mean 'pimp slap' by meaning blasting Galactus with everything he had...and Galactus pulled himself up without being injured or even scratched.
 * The Dark Phoenix is capable of devouring stars and plunging entire solar systems into darkness. And was capable of far more; had she not stopped herself, she could have moved up to X-4. And in at least some What If stories, did.
 * The Dirty Pair have managed to reach most of the levels in this list at one point or another -- only the universe and human civilization as a whole surviving keeps them from a clean sweep. Their current record was set in the comic Fatal, But Not Serious, when an Evil Clone of Yuri used their Cool Ship's Wave Motion Gun to cause a sun to go nova, causing a chain reaction that would destroy other inhabited systems for lightyears around.

Literature

 * Stephen Baxter's Manifold Space culminates in the hero trying the save the galaxy from being "sterilized" by a gamma ray burster, as it has periodically many times before.
 * Likewise, Greg Egan's Diaspora features a galactic threat in the form of two black holes colliding, prompting the main characters to
 * The Krikkit Wars from Life The Universe And Everything rage for 2,000 years with casualties into the "grillions".
 * Vernor Vinge, A Fire Upon the Deep. To stop the Big Bad, the heroes use a weapon that brings civilization crashing down on millions of worlds. Arguably just a very parallel Class 1 or 2.
 * In Larry Niven's Known Space series, Beowulf Shaeffer flies to the centre of the galaxy, until he sees that it's exploding, and our part of the galaxy will be destroyed in some 25,000 years when the radiation hits us. When he returns and tells the Puppeteers, they pack up their entire civilization and flee immediately. (Which makes sense, since they're taking their homeworld with them, and it won't go faster than light.)
 * In the (far, far ancient) prehistory of Known Space, the Slaver Wars are conjectured to have ended this way--with one side or the other building a massive telepathic weapon that killed every sentient being in the galaxy.
 * John Ringo's Into the Looking Glass series features a horde of biological creatures planning to eat the Galaxy.
 * William Hope Hodgeson's The House on the Borderland contains an Older Than Television depiction of the demise of Earth, the solar system, and possibly the universe, all consumed by Chaos and an all-devouring Green Sun.
 * The Deathstalker novels by Simon R. Green includes a superweapon known as The Darkvoid Device. The one time it was activated, it extinguished a thousand suns in a heartbeat. It created an area known, itself, as the Darkvoid, the home of aliens bent on the destruction of all civilization.
 * The Bolo universe has the Final War between the Human Concordat and the Melconian Empire. The war devastated the entire Orion Arm, qualifying as a soft X-3.
 * Isaac Asimov's The Gods Themselves is about a power source which, if not stopped, will blow up the Sun... and start a chain reaction bringing the catastrophe to just below this ("Just below" because it is expected to blow up one of the arms).
 * In E.E. "Doc" Smith's Skylark Series, all of the stars in one galaxy are simultaneously teleported into the same space as a star in another glaaxy, one-to-one, to wipe out a particularly wide spread enemy. The stars with good guys are teleported to safety at the same time.

Live-Action TV

 * The Dakara Superweapon from Stargate SG-1, if combined with the Stargate Virus that dials every Stargate in the galaxy has the possibility of pulling off a Soft X-3. Bye-bye to all life in the Milky Way.
 * Doctor Who's Time War is assumed to be this, with at least five populated planets confirmed to have perished, even if it all went unnoticed for lesser creatures like the humans.
 * In The Sarah Jane Adventures, the Veil Androvax is wanted by the Judoon for destroying 12 planets. As he's a wanted man in multiple galaxies, this may even be Class X-4 scale.
 * After converting her prison ship, in "Goodbye, Sarah Jane Smith"

Tabletop Games

 * In Warhammer 40000:
 * One of the apparent aims of Chaos is to break down the barrier between the Warp and real space. The likely result of this is all of the galaxy being turned into a hellish realm of daemons and skeletons on fire, a galaxy-wide effect of anything up to Class X.
 * If only it was that much of a challenge. According the the 5th edition rules, if the emperor dies then chaos will almost instantly turn the galaxy into hell. No space, no time, only chaos. Yeah, it is that bad.
 * Not only is there the possibility of it happening, it already happened at least once before: the Fall of the Eldar, which involved the Eldar literally Squicking a Negative Space Wedgie from Hell into existence, and wiping out the vast majority of their society across hundreds of light years.
 * Even the Imperium can do this one. Some rare artifacts can apparently induce supernova, and when the wrong people got their hands on the technology, trillions died. Trillions. Wrap your head around that.
 * For reference, the death of trillions isn't much more then a local disaster in this setting... much akin to a Class 0 problem here. Remember, this setting has single planets which host more then a trillion inhabitants. The low estimate as to the total population of the Imperium is around 10 Quadrillion; and it may be as much as an order of magnitude low. The deaths of trillions are tragic, sure, but they're barely a dint in the total population of the Imperium, much less implying the total destruction of the whole galaxy.
 * While the Tyranids don't physically destroy galaxies per se, they do consume every last morsel of biomass in them. And since they're coming straight at the Milky Way from all sides, the only question is whether they finish eating before one of the other factions blows up the galaxy first.

Videogames

 * The Halo series: the titular Halo structures were designed to cause Class X-3s, specifically to
 * A questionable X-3. While the Halos are designed to kill essentially all life in a galaxy, it doesn't destroy the galaxy physically. Everything will still be there, just anything living will die. Planets, stars, buildings, spaceships, sentient A Is, will still remain.
 * Total Annihilation is set at the end of a war that's essentially a galaxy-wide Class 2, with examples of everything else on the scale. The Core Contingency Expansion Pack one-ups this with the Core faction's master plan of destroying the entire galaxy except for one Core Commander, who would then rebuild the Core civilisation. Then in Supreme Commander, two of the three factions are trying to use a superweapon capable of doing this on their opponents. The Cybran plan (which is the canon ending, or the closest thing to it) is to just disrupt the quantum gate network so they'll be left alone, but this inadvertently unleashes an alien horde bent on carpet nuking everyone that's not them. Basically if you live in a game made by Chris Taylor, sooner or later you're gonna get exploded.
 * of Mass Effect cause Galaxy-Wide Class 3/4 Apocalypses that take tens of thousands of years to recover from Species that have  are exempted, however,
 * And in the controversial endings of Mass Effect 3, . And that's not even mentioning the worst endings of this saga.
 * If you lose in Commander Keen 5, not only Earth, but the whole galaxy is blown up.
 * The Zerg in Starcraft kill or "infest" billions of other lifeforms throughout the Terran Dominion.
 * The backstory in EVE Online states that the initial wormhole to Earth collapsed after thousands of starsystems in EVE were colonized, leaving every starsystem stranded without resources for millenia, inducing a technological erosion back to medieval times, where each racial empire had to "rediscover" science and technology over thousands of years of isolation.
 * In the indie video game Gravmari, you play the cause of one of these, a wandering Planet Eater that can potentially grow large enough to devour suns.
 * If left unbeaten for long enough a time, this or Class X-4 would be the result of how Lavos does his work, growing stronger and stronger, by "stealing/copying" the "best" DNA from life forms on a planet, desolating them by method of Class 2, then sending his own "spawn" off to new planets to do excactly the same thing on another planet.

Webcomics

 * Schlock Mercenary's Book 6: Mad Science Means Never Having To Ask "What's The Worst Thing That Could Happen?" concerns a plot by Dark Matter Entities known as the "Pa'anuri" to sabotage a science-experiment in the galactic core -- ultimately resulting in the birth of a new universe, expanding faster than light, and destroying everything it touches. Would, eventually, have destroyed all conventional matter in the galaxy, but it all got fixed via Time Travel. The Pa'anuri destroy entire civilizations on a regular basis by blowing up nearby stars, but are by no means the only big thinkers. The gatekeepers can use stars as fragmentation grenades/gravitic guns.
 * Notably, this explicitly avoided X-4 classification even if it had not been fixed, as the event sealed the Milky Way galaxy off in a bubble universe, which would have contained the new universe's expansion without affecting other galaxies.

Web Originals

 * In QNTM's Ed stories, Ed accesses the root layer of the universe for a fraction of a second, and accidentally wipes out the Andromeda Galaxy. The denizens (those who remain) are not pleased.

Western Animation

 * While on the way to Earth, Futurama's Brainspawn wipe out (presumably countless) planets.
 * Prof. Farnsworth has several doomsday devices, at least one caused a huge supermassive black hole that ate enough stars to spell out "I love you Leela". They also had a star moving machine. The ability to move around stars at will is a pretty significant superweapon in the wrong hands. Good thing the crew are too lazy.
 * The race of Highbreed, knowing they're on the verge of sterility-induced extinction, intend to take every other form of life in the galaxy with them on Ben 10 Alien Force.
 * In the 2011 remake of Thundercats Mumm-Ra does this to.

Real Life

 * Galactic collisions.
 * These do not actually affect the components of the galaxies themselves: Galaxies comprise mostly empty space, and actual stellar collisions are thought to be quite rare. Individual solar systems can be flung out into intergalactic space, however, which if nothing else is a very lonely fate to suffer.
 * Our galaxy, the Milky Way, and the nearby Andromeda galaxy will collide within 3 billion years, merging to form a larger system, very probably a giant elliptical galaxy; when galaxies collide, it's usual that they merge to form a larger one, so it's better see this as a kind of death and rebirth.
 * However, this kind of apocalypse will happen in the very far future (assuming no Big Rip, Big Crunch, or other still-to-be-thought ends for the Universe). After trillions and trillions of years, gravitational interactions between the stars (better said, its dead and dark remmants) in a galaxy will disrupt their orbits, expelling most of them to intergalactic space and approaching the others to the supermassive black hole that lies in the center of most galaxies and that will end swallowing them. Many, many, many years later that supermassive black hole will vanish due to emission of Hawking radiation, disappearing the last trace of what once was a galaxy.