The Bats from Parasite Eve 2. One hit-point, any attack aimed at them kills them... But let them touch you and you are paralyzed for 5 to 8 seconds while it slowly seeps your health point per point... And they come in swarms of ten or more. Preferably at arm's reach. The precognition REALLY applies to this one.
Oddly enough, they're instantly killed with a flashlight attachment.
Also, the Knight/Bishop GOLEM. These cyborgs are not only powerful, but can turn invisible. In fact, they automatically land a hit on you when you first "detect" them, grabbing you from behind without warning and either poisoning you or paralyzing you unless you can kick them away in time. In addition, they use a decoy attack. Fall for it and it guarantees a hit. So not only are you fighting an invisible enemy that swipes at you with the power of a kodiak bear, but you start the fight with a quarter of your health gone and a serious status ailment. What is worse is, while they only show up in the regular game mode towards the end of it, these bastards show up way earlier in the Nightmare and Bounty modes. And since enemies hit for more damage in these modes, if they land two hits on you it's Game Over.
Dead Space has a number of enemies that can prove frustrating, but the Guardian and the Crawler stand out. The former spits out "pods" that explode with considerable force (though, thankfully, not as much as an Exploder) if Isaac gets too close and which otherwise sprout a quill-throwing tentacle and fire at a much faster rate than Lurkers do—and the only way to kill the pod is to sever the tentacle. The Guardian spits out pods at a fairly steady rate, and the only way to kill it is to sever the five tentacles that it attaches to the wall—and which it can pull inside of itself and reattach if it feels like it. Oh, and did I mention that getting too close results in an Instant Death cutscene? Crawlers are small, tend to come in groups, move quickly and can be hard to hit, especially due to their leaping around. Dividers are actually easier to handle then Crawlers; hit the Divider with Stasis, then calmly blast each Crawler component. The Twitcher (due to its speed, random movement and ability to "jink") and the various Advanced Necromorphs, particularly the Scorpion and Lurker, get honorable mentions.
It should also be noted that the whole while, the armless upper torso that is the core of the Guardian is letting out screams of apparent agony the whole while. Not only is it really disturbing, but can prove to be a major distraction while fighting the pods and the Guardian itself.
Swarmers are like ultra-tiny crawlers but ten times as dangerous: They come in gargantuan groups, they stop you dead in your track until you shake them off (and each individual one takes a second or so to shake off, while a dozen more has jumped on you in the meanwhile), and can with their cumulative damage kill Isaac in a shorter period of time than any other enemy in the entire game except for the Guardians. And did we mention that only two weapons are anywhere near useful against them, and one of them is useless for everything else, and the other one you get fairly late in the game?
Don't forget The Pack in Dead Space 2, which can be incredibly irritating on harder difficulties, and Stalkers, which are incredibly smart, as well as fast. Stalkers are capable of playing hide-and-seek, something no other Necomorph can do, and their presence is enough to make anyone's paranoia level go through the roof.
The Leapers get an upgrade in the sequel, now they're fast as hell and kill you dead before you can even finish your girly scream after the thing drops on you from the other side of the map.
Festers in The Suffering. They're bloated, bulletproof slave corpses who can tear open their stomachs to unleash a horde of exploding rats and have a devastating close-range attack.
In a game already the stuff of nightmares with its surprise random encounters which can mystically appear in a room you've been through several times already and often appearing with little or no warning directly in front of you (screaming ensues, if the player is particularly into the game), Fatal Frame has its own demonic spider to fear and fear greatly. The Blind Ghosts, especially in one encounter in a cramped corridor, can turn fear and terror into fear and loathing. They can pass through walls (wherein they become difficult to detect and invincible), move much faster than your character, lunge at you when provoked or if you move (being blind of course means they have superhuman hearing), may not flinch when attacked (this counts as provoking them, naturally), can teleport behind you at any time (including when they're invisible because they're eight feet inside a solid wall, leading to more "AGHHH!" moments when you suddenly catch sight of them less than a foot from your face), and have a nasty tendency to kill you in a single hit. And did I mention they like to counterattack?
The Hunters in the Resident Evil series. They're fast, jump at you from across the room, sometimes team up on you, and have their notorious Deadly Lunge attack that instakills by decapitation. Much deadlier than the literal spiders of the series. And they can poison you in parts of Code Veronica.
Other possibly worse examples: the Chimeras in the laboratory power room of Resident Evil 1 remake (which can also instantly decapitate you), the lickers (particularly the advanced lickers) in Resident Evil 2 (e.g. "caution" status, licker jumps on you from off screen, you die, thrown controller), and the facehugger-like Drain Deimos in Resident Evil 3: Nemesis (at least they don't give you a Face Full of Alien Wingwong).
The infamous poison moths in Code Veronica. Moth lays larva on you, which poisons you, you use blue herb, then go back through the corridor only to get bitten and poisoned again. Whoops, no herbs left, :dies:
There is an infinite-use blue herb tray in the corridor, but good luck using it and then getting back out before another moth can land on you.
Regenerators and Iron Maidens in Resident Evil 4. Both can regenerate (unless you shoot them in the right place) and grab you from across the room, and the latter can kill you instantly.
What about Novistadors? They latch onto you, and must be shaken off, but their attacks do a lot of damage to you while you try to shake them. Oh, and the worst part? They're invisible.
Berserk Dr. Salvador in the Mercenaries level. Can leap to the top of five-story battlements, barely stumbles from all but the most physically devastating attacks, constantly in a state of frenzied swinging of a double-bladed supercharged chainsaw and rampaging balls-out in your direction . Also, those attacks that hurt him? Bring a lot.
The Reapers in Resident Evil 5. They move frighteningly fast and just love to use their unavoidable instant kill attack as soon as they get within range (which is often.) And the best part? They are immune to damage until they randomly decide to reveal their weak spots to you.
They can be damaged - what would "shredding one of its limbs" count as? It just takes an eternity to kill them that way.
Note that hitting one with an electric grenade not only paralyzes it, but also immediately exposes the weak spots. God bless the level designers for placing a batch of electric rounds right before you meet the 2nd one of these. On the other hand if you don't have a grenade launcher with you...
... You use the stun rod. It will make the thing flinch, rip arms off and force it to reveal its gas sacs. If it manages to retaliate, it'll be a slash for minimal damage. Hell, you can even bash it to death with it alone. You can't let up on the offensive, though, or it'll recover.
The Eliminators from Resident Evil Zero. You'd think a zombiemonkey would be an awesome enemy, but holy shit would you be wrong: they're extremely small targets, ungodly fast in both attacking and avoiding your shots, deal significant damage in a small amount of time, nearly always attack in groups of three or more, tend to appear in open areas with lots of room to get behind you, and they take a minimum of three shotgun shells each—each!—to kill. Compared to these nasty little fuckers, Hunters are about as troublesome as a mild sneeze.
Not if they are alone. And they're severely watered down in The Umbrella Chronicles.
What about the Plagas from Resident Evil 4? These damn things spawn at random, always emerge from their host when you kill them no matter whether you deliver a headshot or not, suck up more ammo than the actual Ganados themselves, and the type 2s have the ability to bite your head off if they get too close, which translates into instant death. True, they have a Weaksauce Weakness ( flash grenades kill exposed Plagas instantly), but it's not exactly obvious. And, worse, type 3s (the spider/bat ones that detach and start fluttering around on their own) take two hits by default; one to make them leave their Ganado, and a second to kill them.
The Cerberus dogs throughout the series. They are difficult to hit with the clunky aiming controls and lock-on, and usually attack in pairs or more, so while you're attacking one, the others can get the jump on you.
Unless you use auto-aim and are smart enough to either trap them in a narrow bottleneck corridor or put yourself back against a wall. Then you can unload on them pretty much with impunity until they die.
The Outbreak series has a couple as well, from the Hunter Rs (all the fun of the normal Hunters), to the Wasps (only Goddamned Bats if you have a handgun, which is no guarantee by any means). The Lionesses from the "Wild Things" scenario are the worst though. They have a tendency to attack anything in melee range when struck, they can chase you down with little trouble and they soak up a lot of damage, wasting bullets for the scenario bosses. And the best part? An instant-kill pounce. You have plenty of warning before that one though.
The Crimson Heads in the Resident Evil 1Remake are also a serious pain if you do not burn the dead zombie bodies (or blow their heads off) before they can come back as Crimson Heads, they can run as fast as your character can, do a decent amount of damage, and even worse will sometimes not get up from the ground until you walk right over them. And there is not enough oil to burn all of the zombies in the mansion, so sometimes it is simply best to let the zombies live in order to avoid them turning into Crimson Heads.
Therazinos from Dino Crisis are not only insanely strong, highly dangerous and -thanks to their traveling in pairs- nearly impossible to bypass, but they're also given their own Press X to Not Die cutscene which makes you think they're a one-off Dual Boss. Nope. They're a regular enemy from that point on! Be warned: save your poison darts or get ready to snap a few controllers dealing with them.
The Shibito in Siren are giggling, bloody-eyed Japanese farmer zombies who somehow manage to pop you with a headshot from across the map through a copse of trees if you make even the slightest error in traversing the level. Apparently becoming Shibito imbues one with the accuracy of a Navy Seal sniper. There's some good news, though—you can actually survive one shot to (hopefully) dive back into cover... and you can use sightjacking to tell exactly where they're looking and when, so you can stay the hell out of the way. Also, not all of them have rifles—although some of the ones that don't are nearly as bad.
For an example of "nearly as bad," look no further than the Crawlers. Their melee attacks can kill you in two good hits, depending on the character—the same as a gunshot, for reference—and they're fast and particularly alert and difficult to hide from. Oh, and some of them can walk on walls. The plus side is that since they move on all fours, they can't open doors... and they're usually found in the presence of a shibito brain, which will knock them all out at once if it's taken out. The bad news there is that shibito brains are Goddamned Bats, due to their tendency to be able to tell you're there without seeing or hearing you, then run away quickly.
Let us not get started on the flying Shibito, who are essentially snipers with wings.
Schisms, Needlers and Swarms from Homecoming, Victims and Wallsnatchers from The Room, and on occasion, Straitjackets from 0rigins. Honorable mention goes to Creeper and Hanged Scratcher from the original.
The nurses, particularly in the third game, the Abstract Daddy monsters in the dark and narrow hotel corridors, and the Slurpers, which can knock you down again immediately after you get back up, repeat until death.
The Smogs from the same game. Not only do they have a ton of health, their attacks can only be dodged by rolling away, as they can stun you with a smoke cloud that is unavoidable (and does damage). Also, if you can't break out of it, they knock you down, dealing even more damage. While it's easy to run past them, they are also the only enemies to have a ranged attack, and very damaging one at that.
Crawlers are this to Cold Fear. It takes a full clip of shotgun shells to kill one, and they are fantastically speedy and stealthy wall masters. They have a nasty habit of jumping on to the ceiling and hiding in a ventilation shaft after you have damaged them, then reemerging from a different ventilation shaft elsewhere in the same room so they can sneak up on you.
Also, their Weaksauce Weakness was supposed to be a fear of bright light, but that really just makes them wander off so they can attack you from behind later.
After its transition to 3D, The zombie MMO Dead Frontier added several "Boss" zombies throughout the maps. Pretty much the only ones of them that aren't an example are the Bones (which are only moderately more powerful than normal zombies) and the Brutes (which are ungodly slow and whose main gimmick, exploding upon death, is easily avoidable with ranged weapondry). The rest? Oy...
The Reapers and Tendrils will oneshot low level players easily with their insane melee attacks, and the Tendrils in particular have a massive attack range.
Sirens don't even have any actual attacks, and yet they are the bane of many players because as soon as they detect you, they emit a scream that alerts pretty much every single zombie in the area to your location, with predictable results.
The Spiders are ungodly fast and nearly completely immune to knockback.
One of the more recent updates added Burning Zombies to the mix. They are as (if not more) fast than the Spiders, always spawn with maximum aggro (which means they home in on you at top speed) and, contrary to what you may expect from a Man On Fire, they have a massive amount of health. On the plus side, they tend to drop mid to high tier loot when they finally go down.
You can kick some major ass when the deadisrising, but then the gas zombies come, you're gonna have a bad time. To elaborate, most of the campaign in the second game has you dusting easy-ass zombies with all sorts of incredibly fun combo weapons. But once you get far enough in the story mode to the point where the military comes to the rescue and things go terribly, terribly wrong when the zombies are exposed to an odd gas. They become a hell of a lot more resilient, they get fiercer and stronger, and can now charge at you at an alarming pace. If a gas zombie grabs on to you, you have to do a mini quicktime event to shake them off, and you will lose quite a bit of health in the process. They can also vomit up a foul substance that will root Chuck in place and cause him to cough, helpless for any follow-up attacks. And did I mention that they love to gang up on you in large groups? You better be at a good level and have intricate knowledge of how to put together the best combo weapons, because these suckers don't mess around. Their horrific strength is even acknowledged in universe, as they completely annihilate the military convoy that was meant to rescue the Fortune City outbreak survivors, and drive the CO in charge mad from the carnage he is exposed to.
Speaking of powerful Dead Rising 2 enemies, the True Eye cultists and Spec. Ops soldiers are much, much deadlier than the Willamette Mall's many zombies. The cultists are more often than not found clustered in huge groups praying, blocking off pathways until they notice you. They can shave off huge amounts of health with their knives, do a suicide attack at low health that you cannot stop, and can stun you with holy water and cart you off to their hideout, where they proceed to remove all of your weapons and clothing and will force you to kill the group watching you to get back into the mall. The Spec. Ops on the other hand are armed with powerful machineguns and like the cultists, they can knock you out if given a chance and take all of your belongings. Both are more resilient than zombies as well, with the Spec. Ops being even harder to kill than the cultists.
Back on the topic of the second game, the Phenotrans mercenaries are much deadlier in the re-release Off the Record due to the fact that rapid-fire guns are now capable of taking off health at an alarming rate instead of flinching you and giving you brief period of mercy invincibility like in the original game. You will run into them EVERYWHERE in the end-game.
Out of the four or five, if you count Golden Freddy animatronics from Five Nights at Freddy's, Foxy can be leaps and bounds tougher to deal with than the manageable Bonnie and Chica as the method for dealing with him is unique: you need to keep watch over Pirate Cove, the area he resides in because if you aren't watching him enough, Foxy will bum-rush your location and leave you with maybe a second to shut the door before he kills you. And worse, even if you shut the door on him, he'll bang on it a few times and drain you of your power. The only way to keep Foxy from messing up your strategy is to make sure you regularly check up on him.
Freddyhimself is even worse. Not so much on the first few nights where he isn't even active and only comes to kill you if you let your power go out, and even then it's still possible for him to take too long and accidentally allow you to survive the night. But from Night 4 and beyond when he actually comes out to play, he doesn't screw around. His movement pattern is hard to predict, and seems to be based off of specifically countering strategies that the player deployed during the previous nights. Unlike Bonnie or Chica who are easily found on-camera, Freddy is for the most part much tougher to spot, with the only camera he's easily found on is the one closest to your office, and at this point you have seconds to react before he gets you. He's not like Bonnie or Chica, who both hang around outside of your room before moving in for the kill, he goes straight in to murder you. And the cherry on top of this terrifying sundae? If you shut both doors, he somehow teleports in anyway.
On later nights, the older generation of the Fazbear game comes out to play, and unlike their Toy incarnations, they are a lot harder to deal with as you pretty much have to put on the Freddy mask on right away when they show up in your office. If you are even a tad late in reacting, you will die.
On the PC version of the game, Mangle is no more harder to deal with than any of her Toy Animatronic friends. However, she can be a lot harder to deal with on the mobile port because of the failure to carry over the only way for you tell if she's near you. In the PC version, she makes an incredibly creepy garbled set of radio noises if she's close, which ought to prompt you to deal with her. In the IOS version? These noises didn't carry over, and if she gets on the ceiling of your office, she WILL kill you, and there's nothing you can do about it which can lead to some cheap, unfair deaths.
Balloon Boy may not actually kill you himself, but that doesn't make him any worse to deal with. If you don't put on the Freddy mask fast enough, he'll get into your office and disable your lights, and laugh at you like the little shithead he is. This not only keeps you from looking inside the vents, but will keep you from using your flashlight to see if any approaching animatronics are coming, namely Foxy who ISN'T fooled by your Freddy mask. Worse, he won't go away, so you better hope the 6 A.M. is approaching if he gets in, because you're pretty much animatronic bait.