Serious Sam's kleers. Not only are they obnoxiously numbered - far outnumbering anything else in the game - they perform a heavily damaging lunge attack (enough to kill in three or four hits on medium difficult) that is hard to dodge - and even harder to dodge when the kleer right behind it launch right at you. Worse is that they soak up a ton of damage - requiring a point-blank double-barrel shotgun blast to kill, a maneuver not advised.
Pretty much every cop in Mirrors Edge exists solely for the purpose of interrupting some otherwise fun parkour platforming. This applies especially to the ones that you have to kill to move on, despite the fact that you have no body armour and are totally unarmed. And they have fucking machine guns.
Unreal has several. The most widespread are probably the pupae, four-legged spiderlike critters (actually embrionic Skaarj) who don't do any significant damage with their lunge attack and are slow, weak and easily targetable to boot, but make an extremely irritating hissing/tapping sound that'll have most players instantly go "OHMYGODWHEREISIT DIEDIEDIE!!". A similar effect is caused by the flies, as their threat level is practically insignificant but their flying noise is scarily reminiscent of actual insects.
Unreal: Return to Na Pali features 1-foot tall creatures called "predators". They always attack in groups, run at least as fast as the player, and have a tendency to appear out of nowhere. On top of this, their hit-boxes are far smaller than their actual models, so things that SHOULD hit them end up missing entirely. They also have a full 100 Hit Points despite being only a little bigger than the Nali Rabbit, which dies in one shot from anything.
The Quake series has quite a few, monster and alien alike:
In the first game, you have Scrags and Grunts, enemies that are relatively small and often use the cover of other enemies to get in a potshot at you. Knights are relatively weak, but take enough time to kill that it's likely that they'll get at least a bit of damage in with their running attacks when you encounter them.
II has the Fliers, small gunships that are pretty hard to hit, fire off a rather damaging laser stream, and make an ear-splitting sound as they hover. They share these traits with the Technician, which is only different in that it's larger and has way too much health for an enemy of its caliber (almost the same of the genuinely threatening Gunner). One of its melee attacks, an electric prod, hurts you even if you run far away from it. Barracuda Sharks distract you when you're in the water, often making you lose at least a few hit points by drowning, and have quite the damaging bite. Shotgun Guards are another Glass Cannon kind of foe, especially in groups, made worse by their unusually accurate shots.
The Reckoning has Ripper Guards, who fire a three-shot burst of projectiles that can bounce off walls, and Laser Guards, whose beams distort your vision and lower your accuracy. Enforcers also get promoted to this, as they don't have to cock their guns before firing. And finally, the Gekks, who do as much damage with their ranged attacks as the pitifully weak Light Guards, but have the health of a Gunner and the behavior of a mix between the Berserker and the Mutant (they can get in close pretty quickly and dish out lots of pain witth their claws). The worst offense about them is that you meet these buggers almost exclusively in dark caves, where you'll often be using your Blaster as a flare gun to light the way.
The Doom series has a full banquet of these to choose from. Pick your poison.* There's one interesting exception, however: the addition of the grabber in Doom 3: Resurrection of Evil effectively neutralizes all of the bats in the game, as it will pick up the smaller enemies for an easy One-Hit Kill, although this does afford you some unattractive closeups of the critters. Cherubs in particular are an effortless kill with the grabber.
The Lost Souls in Doom and Doom II. These nasty little flying skulls are even more of a pain in the original because your main weapon for close-up killing, the shotgun, takes two blasts instead of one to kill each one, which doesn't exactly help when you're wall to wall in them. In the latter, they could be infinitely produced from a Mook Maker aptly called the Pain Elemental, but at least you have a Double Shotgun that can kill the little buggers in one blast.
The imps are probably a straighter example. By themselves they represent a risible threat, as their ranged attack is very slow and easily avoidable, they take ages to close to melee range and they go down with a single shotgun blast. But the bastards are everywhere, and when in significant numbers they like to swarm you with so many fireballs avoiding them all is impossible. It's rare to get killed by imps, but they're massively annoying.
The Lost Souls in Doom 3 are even worse, as they tend to fly in random directions when not charging at you, making them a pain to shoot down. Their ram has a ton of knockback too, so you might find yourself plummeting to your doom if you don't watch the ledges when fighting these guys... which leads us to their finest bat moment: in the Hell level of Doom 3, where they get lots of chances to knock you off of the floating platforms into a bottomless pit. Fortunately they won't show up if you avoid jumping on the platforms that trigger them.
Don't forget Ticks/Trites. Individually, they're a matter of two or three pistol bullets to kill, but in large numbers and tight spaces (such as That One Corridor in post-Hell Delta Labs), they are an absolute nightmare.
Also the Cherubs. Dealing an uncalled for dish of distilled hurt for their size with their claws and being horrible to hit with anything that isn't the plasma gun, these buggers would be a pain even if they didn't make those distorted child-like babbles that are widely considered by the fanbase the game's Nightmare Fuel of the highest octane.
First, of course, are The Flood. The sequels add Drones (swarms of annoying flying things that WON'T DIE), and sniper Jackals.
Many of those, of course, cross the line into Demonic Spiders territory on Legendary. Especially the Flood in the later levels of Halo 2 and 3(their melee attacks kill you instantly). And those "Demonic" Drones. Try to hide from them, they will swarm your position from all sides and render you a plasma-carbonized corpse.
The worst is basically EVERYTHING in the Library level of Halo 1. There's goddamned millions of Flood forms and you have to kill every. Single. Last. One. Meanwhile, 343 Guilty Spark annoys the hell out of you. They come from freaking everywhere, making it difficult to put your back to a wall and nigh-impossible to avoid getting blindsided. Add in the fact that every part of the level looks the same and it's very easy to get lost.
Those Ultra Elites have an ungodly amount of shield energy, are resistant to assassination and plasma grenades, and regenerate almost instantaneously when they take cover. Can be Demonic Spiders on Legendary, where they can kill you instantly if dual-wielding plasma rifles, and can berserk with the lethal plasma sword.
The sniper Jackals all go from Goddamned Bats on Easy through Heroic and straight to Demonic Spider territory on Legendary, when their sniper rifles will always instantly kill you and even their weaker carbines will tear you to shreds. The regular Jackals (with the shields) are just your default annoying-but-useless enemy on every difficulty.
Halo 4 introduces two other types of Promethean battle droids to complement the Knights. The first are Crawlers, fast little buggers who love to attack in swarms, and can easily wolf-pack you to death on higher difficulties. Also, a few of them have Binary Rifles. The others are Watchers, airborne enemies who are small and fairly agile. They can summon Crawler packs or heavy autoturrets, can throw grenades back at you, can form hardlight shields to protect Knights, and can even resurrect freshly-killed Knights. It's in a player's best interest to always kill Watchers first... which can be tough, as they will start flitting around once you open fire on them, leaving you frantically trying to track them and deal enough damage to destroy them while Crawlers swarm you and/or Knights gun you down.
Seeker remotes. The thingy Luke practices lightsaber skills with in the first movie. They weren't powerful, they weren't tough, and they would require a day or two to actually kill you, but not with a blaster pistol, a lightsaber, a rocket launcher, or a plasma cannon was there an efficient way to destroy those little bastards. It took either a lot of time, ammo, or luck to take them down, even with the games' auto-aim feature turned on. In most of the games, by the time you got probably the only efficient way of killing them (full-power Force lightning), they either didn't appear anymore or that particular game didn't give you lightning anyway. Thank the Force they were rare after the first game (and that you could use them as weapons yourself in the second).
Dark Forces also had bats in another form: mines. Innocuous little disks, they had a proximity sensor and left off a boom bigger than a thermal detonator when you got close enough. A clever player could turn this against his enemies... when he knew the mines were there.
Jedi Outcast also deserves a special mention for a few... inspired inventions. First, the little critters with teeth in the Kejim missions, which were tiny and so hard to hit with anything approaching accuracy. Thankfully, the stun baton was efficient at dealing with them... but if they'd stuck with bare hands as your backup weapon until you got the lightsaber, it could have been a lot worse. Second, the Rodian snipers in the Nar Shadaa and Cloud City missions. They were worse than sniper enemies in other games because if you tried to snipe Force-sensitive enemies with the same weapon, they would dodge (the weapon's shots couldn't be blocked by a lightsaber)... but did you get such an ability, despite being a fairly powerful Jedi? Nooooo (most of the time).
In Jedi Academy at least (which has nearly identical gameplay to Jedi Outcast) the ability to dodge energy missiles for the player character exists but is not described in the manual and is activated in such an obscure way it can take about ten times of playing through the entire game to notice it. Apparently you have to stand very still and be shot at for it to activate, possibly with your lightsaber off, too.
Also, if you hold alt and left/right, you can do the dodge yourself. If you do it the right way, you don't even have to time it. It actually is in the controller configuration, hidden as a little side note. Very useful against those annoying snipers :) Also make sure you never run out of The Force, most of your deflecting and stuff gets much worse when you're dry...
The thermal-detonator-tossing Grans that show up in several of the Dark Forces games. They have perfect throwing aim from absurd distances, never run out of grenades, and (in Jedi Knight at least) they appear as early as the second level and are completely indistinguishable from their rifle-wielding and fistfighting brethren until they start chucking explosives at you.
Heretic II featured heavily annoying "Harpies," essentially gigantic bat things. It wouldn't be so bad if it weren't a third-person game and therefore featured imprecise aiming, and even your most powerful spell could be easily avoided, as they could strafe in mid-air.
Every House of the Dead game has zombie bats as enemies, but House of the Dead 2 adds to the madness by having the even harder to hit zombie owls, which fly on screen and then automatically head straight for the player in a kamikaze rush.
Half-Life 2's Antlions. Especially in the levels where they respawn if you even so much as look at sandy ground.
The worst part about Antlions is that they have an annoying habit of pushing you off of your little island and make even more of them appear.
The Scanners also definitely fall into this category, as they have an annoying habit of flying in your face and blinding you. They have an uncanny knack for doing this exactly when you really need to focus.
Usually "When you really need to focus" == "when you're hiding from a Strider". Which the Scanners can alert. Dammit.
The regular and fast Headcrabs, which jump all over the place and frequently end up behind you, often behind furniture. They don't do much damage or have much health, but they are very hard to hit. The poison headcrabs, however...
The original Half-Life and the Alien Controllers. Little guys with big heads that fly around flinging electricity orbs with great accuracy and screeching creepily. They're much harder to take down than they appear at first. Thankfully, they only show up during the final levels of the game.
In the Source version they do literal strafing runs, flying so much into your face their model clips.
Also, Barnacles. Game: original Half-Life. Part: "Forget About Freeman", swimming stretch. After you finally get through the game's last leeches, you pop up to take a breather... RIGHT INTO A FUCKING TENTACLE HANGING FROM THE CEILING. Source games are even worse since Barnacles can now drop their tentacles into the water and deep water is always murky. Face it, Valve mastered Paranoia FuelUp to Eleven.
Manhacks certainly qualifiy: small? check. flying? check. minimal damage? check. attack in swarms? check. fortunately, they don't show up very often.
Hell, you know what? Original Half-Life had those FUCKING LEECHES. Why? Their small damage quickly adds up (in the original, one point per bite; in the Source version, five points per second), they instantly swarm you AND the fact that their hitboxes physically block your way which is an utter bitch during long swimming sessions. And their wriggling is just plain creepy. Most of your weapons don't work underwater either. It is said that by the time of HL2, leeches spread out into the ocean and bred to the millions, eating all marine life. Thank God we don't have to go in...
Half-Life also had the snark nestings. Small, fast, noisy and exploding.
S.T.A.L.K.E.R.'s hound-like enemies epitomize the Goddamned Bats. They are extremely difficult to hit due to their random movement, small size, and instantaneous 180-degree direction-change; travel in swarms; offer absolutely no reward upon their deaths; block your movement by swarming around you; and, worst of all, frequently appear at a bottleneck between you and a place you really need to be, most often when enemies are already at your back.
The worst of the lot are the Psy-dogs: extremely fast, agile Mook Maker pseudodogs that generally hang back, spawning an infinite number of illusionary copies of itself that are very hard to tell from the real thing, charge you in packs, and can still hurt you despite being illusions/hallucinations. Incredibly irritating, forces you to waste ammo that's often already in short supply. The only redeeming quality is that all the "projections" die when the real one does.
Bandits are also extremely annoying. While their body armor consists of little more than a black jacket and ski mask, and their weapons are hands-down the worst in the game, they can be found in virtually every single area, are always hostile except when in the second game (and even then, you'll run into groups that randomly shoot at you, when the "neutral" ones aren't mugging you of course), and they always manage to hit you with at least one bullet. Sure, their Makarovs do about as much damage as a kitten once you get a decent set of body armor, but when there's five of them at once...
Not to mention that as noted their gear ninety-nine percent of the time is merely substandard at best, and you'll rarely be carrying weapons that use the same ammo as their weapons (with the exception of any shotguns). So the most you'll usually get off one of the bodies of an entire group is a few bandages or medkits, and most of the hardware is left right where it is due to weight concerns. To sum up - you've probably wasted a few magazine's worth of ammunition and a couple bandages and/or medkits, and even with whatever you manage to yank off the bodes, you're still looking at a net loss.
System Shock 2 The Goddamned Monkeys. They start out shooting Cryokinesis bursts at you, which then turn into Pyrokinesis bursts that do more damage. They're so small that they're a real pain to hit with your wrench, and they scratch when you get close, dealing a surprising amount of damage for tiny monkey hands. They're everywhere, and you can hear them chattering a mile away. Unlike the spiders, they can shoot you from across a huge hallway...or that section of cargo bay filled with them.
The spiders deserve mention however, as very tough creatures, resistant to regular ammunition, who infect the player with a poison that never goes away on its own (and in fact it is possible to get into a situation where there is no way to access an anti-toxin hypo before you die) and toward the end of the game are nearly invisible, especially in the dark (and there aren't many brightly lit places in this game). Also, you know, they're f-ing spiders!
Hope you saved enough bullets to deal with Protocol Droids. Wrench combat being annoyingly risky and slow, you're going to be using ammo... and then these guys come along, who explode upon entering melee range.
Dead Space: Extraction includes inch-high swarms of Goddamned Bugs. They have no annoying qualities (other than being small and in groups), but can be dangerous if a bunch of them manages to latch on a player.
In the original Descent series, there was the Thiefbot. This nasty little creature would come sneaking up on an unsuspecting player (typically in the middle of a fight with other enemies), zap you with a special shot that made your view go all wonky, steal some powerups, and then zip off to the furthest corners of the level in an erratic evasion pattern.
The Thiefbot has the distinction of being the one enemy in the game who can't actually physically damage you at all, but also probably the one you'll be expending most of your firepower (and profanity allowance) on, as it's among the fastest and most heavily-armored robots in the game. Normal enemies you target and hit smartly while trying to be efficient with ammo/energy usage and to stay behind cover, but a Thiefbot generates such hatred that most players will drop whatever they're doing and initiate a wild chase through half of any given level to get a vital weapon back, making desperate potshots, indiscriminately firing anything available and trying to chase it into minefields.
What's worst about the Thiefbot is that if it managed to steal from you more than once, the weapons it first stole will most likely not be returned to you when you destroy the bot.
And there were the ITDs (which can summon larger robots), Sidearm Modula (blinding flash missiles), Hornets, ITSC, Seekers (outright Demonic Spiders, in fact), etc.
The Internal Tactical Droids are a particularly clear case of this trope. Their weaponry was incapable of inflicting much damage per hit, but they consistently employed the tactic of sneaking up, hitting you once, and then fleeing evasively to the uttermost parts of the level. Thing is, you had to hunt down, corner, and kill every single one of them (and lo, there were many), because otherwise they'd open some door at an inconvenient time when you had your back to it and expose you to heavy fire from who knows what. On some levels picking up the yellow or red key when there were still ITDs loose could actually be suicidal due to this phenomenon.
Descent 3 pits you against little purple shark shaped robots that only deal melee damage. Their primary source of nutrition must be your ships shields because they eat right through them. And did I mention they are only about a quarter the size of your ship, move very fast, and have a tendency to come running from three rooms away?
To sum it up: The line separating this trope from Demonic Spiders does not exist in this game series.
Resistance 2 has the Chimeran drones, which are really annoying - they fly about and are hard to hit, distract you when there are worse enemies around, and can't be dodged. Some of the other bots listed here.
Many flying enemes in Serious Sam 2, especially small floaters and witches. In multiplayer it's more apparent.
Serious Sam 3 has space monkeys which are usually fought in areas with lots of pillars. They jump from pillar to pillar and hiding behind them, occasionally lunging at player.
Return to Castle Wolfenstein: Those damned Femme-Nazi Elite Mooks in the church mission. On the "Death Incarnate" difficulty, they become outright Demonic Spiders.
Marathon has the Wasps, which come in enormous packs, hide around corners, and fling corrosive spit at you from huge distances for minor but irritating damage. They tend to lurk in niches not at eye level, and they take three shots from a handgun to kill. The Fusion Pistol can dispatch these in one shot, but they have a silver form that takes two hits even from that gun to kill.
The common infected in Left 4 Dead have this wonderful ability to slow your movement speed when they hit you, which is so effective that if two of them are attacking you at once you're practically immobilized. It makes it great fun when you're trying to run away, or heck, even just walk across the room, when you CAN'T FREAKING MOVE because no matter how many you kill, more of the bastards keep trickling in and slowing you down or just physically blocking your path.
The sequel makes this even worse where the AI for the common infected are smarter by running to your side or behind you as the rush to you and attack while you flail or shoot like mad and miss because the infected just practically slide around you and flank you on all sides.
The sequel also introduces uncommon common infected, which are common infected with a gimmick. Hazmat infected are immune to fire, but are not a big deal. Clown infected attracts nearby infected do you with its squeaking shoes if it spots you, making it almost like a mini Boomer. Mudmen infected are one of the most annoying ones where they run on all fours to run faster and are not slowed down by water, plus when they hit you, they splash your screen with mud. Worker infected can take some more bullets than a regular zombie due to their protective work gear and they also wear headphones that blocks out noise so they can't hear a Pipe Bomb (because of lazy coding, they will also ignore Bile Bombs due to it using the same attraction script as a Pipe Bomb). The Riot infected is one of the more annoying ones where they wear body armor and are almost unkillable in the front but are weak in the backside. Most players will shove a Riot infected to stumble them so that they can run to their backs and kill them, but if you are in a narrow hall or push the zombie into a corner, you are going to have a hell of a time trying to kill them.
The Scout, of Team Fortress 2 fame is found to be annoying by many players. Quick, hard to hit, damaging — yet not a primary attack class, and so seen as an irritation more than a threat. His dialogue can be quite grating. Like many Goddamn Bats you don't want one close when you are wounded. (Hilariously enough, if said Scout chooses to use his melee weapon, then you might have a literal case of Goddamned Bats on your hands.)
Not to mention his high speed and double jump make him ideal for exploiting weak spots in the defense of the enemy team to grab the intelligence or capture a point (he also captures points twice as fast as anyone else).
The Pyro can also get this reputation, especially in tight quarters. If the high damage of the flamethrower doesn't kill you, the afterburn might kill you just steps away from a healthpack, dispenser, or water.
The Engineer received the Combat Mini-Sentry in his update which is basically made of this trope. It deploys fast, is cheap enough that the engineer can drop another one when it's destroyed, fairly small, and still lethal enough to kill most classes (and shut down certain classes, like Scouts) if the element of surprise is still there.
Minor League Scouts in the Mann vs. Machine mode count. In addition to being based on regular melee Scouts, which are annoying enough, they also can throw baseballs, which can stun the player for long enough to let others overwhelm them, or even deliver the bomb.
Uber Medic robots are also a pain- unless you can destroy them in one hit, they will always deploy their Ubers (and spawn fully charged) when they take even a scratch's worth of damage. Even worse considering in this mode, the enemy can carry and deliver the bomb while Ubercharged.
Starting around early 2014, the popularity of a video by STAR_ led players to start using the Soldier's Rocket Jumper, Mantreads, and Market Gardener and leaping about the map like eagles on pogo sticks, landing only to immediately take off again. Done well, they can be effective at surprise attacks. Done poorly, they can be even more effective at distracting enemies and royally pissing them off.
The Shock Troopers from Killzone 2, all three types. They run around, stay behind cover while hitting you with walls of lead and grenades and they never come at you alone. A lot of players tend to die quite a few times against these guys.
Will Rock has Goddamned Rats... Explosive rats. Small, blazing fast, hard to hit, and chase you relentlessly. There's a level where you are assaulted by dozens of them, but thankfully it's in a wide, open space; much worse when it happens again, in a much smaller circular hall.
Also the basic axe-throwing enemies. Not so much because they deal much damage (they don't), or because they're hard to kill (they aren't), but because when they die they go through an animation that eventually causes two lesser enemies to spawn from their remains. You can't ignore them or they'll start chipping away at your health when you turn your back, and you can't kill them before they spawn, so every one of the original baddies you kill requires you to wait a good few seconds for the split/spawn animation to finish.
Lurkers, for those who have played Metro 2033. They're fast, take out a good chunk of a clip, and can dissapear into their little rat-holes at any moment after gnawing the protagonist's kneecaps off. Add to that the fact that they tend to respawn endlessly and their rat-holes double as instant-kill deathtraps and you have goddamn mutant Russian rats.
Borderlands Goddamn Rakks. Spiderants and the Bandits probably count too.
Spiderants deserve a little more explanation: Where there's one, there's fifteen others ready to ruin your day, and you better hope none of them are elemental badasses which are downright Demonic Spiders (no pun intended). The major problem with Spiderants is the fact their front is covered by a very thick shell that render most of your weapons nearly useless and trying to go around it to Attack Its Weak PointFor Massive Damage is tends to be problematic since there are variants of Spiderants that a) try to sneak on you or b) shoot you from afar.
Defilers are the only zombies who operate solely at range, spitting bile at you that obscures your vision and slows your movement, making you a sitting duck for their zombie pals. Corpse Eaters are even worse than Rakks who will attack, retreat and give you some room to line up a few shots. These bastards will swarm twelve at a time, continuously circle, locking you in place and pick players apart. This is all assuming you don't have a Tankenstein breathing down on your head.
Borderlands 2 adds Stalkers, stinging lizardlike creatures that go obnoxiously invisible.
Stalkers, and really, most enemies, become Demonic Spiders in True Vault Hunter Mode. Rabid Stalkers and Skag in particular move obscenely fast, hit like tanks, and take a crazy amount of damage to kill.
Also Surveyors: while they don't have much HP and can't deal as enormous amounts of damage as many other enemies, they have a few traits that really make them annoying: 1. They're small, flying targets, which make them incredibly aggravating to shoot down 2. they have the ability to repair and/or create shields for robotic enemies, which can drag out many fights longer than you'd want them to be. The developers were well aware of this; one of the loading screen tips is "Surveyor bots repair injured Hyperion loaders. You will learn to hate them."
Operation Body Count has the goddamn rats that make up the majority of the first 5 levels and continue to appear throughout the rest of the game. one or two aren't an issue. 4 or 5 might make you worry. 10 to 20 of them coming at you at the same time is when you start bringing out the uzi and doing the old "Spray 'n' Pray". Oh, and they come in to sizes: Small minor nuisance and Giant notable nuisance. And since the annoying parts of the rats carry over to those shock drones...
Duke Nukem 3D has its fair share, but the little oozes that grab your face (blocking the screen doing so) and the self-destructing kamikaze drones stand out the most. The drone even has an appropriately nerve-wracking noise that'll have you jumping on your seat and then searching the entire level until you find and destroy the bastard, just because you know if you don't it'll smash in your face and explode when you're least expecting it.
Likewise Duke Nukem Forever has Octabrains, who tend to attack in swarms of two or more. They fly, they're incredibly agile, and if they're not throwing things littered around the game environment at you, a blast of their energy ball can knock helluva lot off your Ego bar. And did we mention that they can grab large ammo projectiles you fired (say, RPGs, devastator rockets or your pipe-bomb) and hurl them back at you? And fighting them underwater just makes things more difficult.
In most Call of Duty games the most irritating enemy you would have to face are dogs, they easy to kill but they run fast, and almost hard to hit. When they get to you, you have a small chance of stopping them from ripping out your throat.
In Black Ops II, enemy Quad drones can be a huge nuisance, on account of being small, nimble targets that flit around and pelt you with machine gun fire from all angles while most likely dodging your attacks. It's especially bad in Strike Force missions, wherein swarms of them can show up more than once in a given level. ASD's and CLAW's, at least, are obvious threats that you can single out and destroy as soon as they show up. Quads, on the other hand, can and will hang around for quite a while and harass you while you try to fulfill your objectives.
Star Wars: Republic Commando's second level introduced Scavenger Droids, little flying metal droids that filled the player's screen with static as they drew nearer, moved constantly to avoid being shot, and whose favorite form of attack was to attach themselves to the player's helmet and carve through it to attack the player's head.
Also the Magna Guards that showed up towards the end of the game who would jump, flip, and dodge all over the screen and could take quite a few hits before going down.
In Killing Floor, the crawlers aren't very difficult to kill, and they don't do very much damage alone. The only problems is that they attack in swarms of 4-6 at a time, and they jump, and they're about a foot-and-a-half tall. They're also textured black, so in the dark they're difficult to spot. They have the annoying habit of blocking your way when running from fleshpounds or improbable swarms of enemies, and if you encounter them on stairs expect to bounce around like a goddamn rubber ball. They're the absolute worst for the melee class, as berserkers often have to crouch and ignore every other enemy just to have a chance of hitting them.
Singularity has the goddamned Phase Ticks. Not only do they inflict high damage, but they also inflict fear on the player. These things are like suicide bombers and you are the towers. If that's not enough, they appear in huge swarms and are COMMON. Consider yourself cornered having 5 of these near your vicinity.
Sniper Elite: Enemy snipers. They have a nasty habit of taking potshots at you and hiding before you're able to target them.
Carnivorous fishes in general often seem to be this in First Person Shooters, since they're usually small, tend to come in swarms, and are fought underwater - an environment ill-suited for classic FPS fighting (since they can come at you from up and below, and you need to mind the oxygen running out).
EYE Divine Cybermancy has the Perigrum Forma, small leaping things that look vaguely like Aliens. They are rather weak, but they are hard to hit and spawn en masse.
Mecha levels in Shogo: Mobile Armor Division have human enemies. They're pathetically weak and have no armor whatsoever, so any weapon at all will kill them in one shot - as will simply stomping them flat. Good luck finding them, though, as their minuscule size, dark clothing and trailless weapons allow them surprisingly good camouflage. They are little more than an annoyance singularily, but as you laboriously find the little buggers they'll whittle down your health enough that the next mecha you meet will have a rather higher chance of smacking you down.
Commandos, Ravens, and Cicadas in MechWarrior Online that are equipped with the ECM upgrade went from laughably bad models of mech to just plain mean. It turns a poorly armored little cannon-fodder mech into a monster that can make a team of Humongous Mecha disappear, due to the fact that ECM interferes with the ability to lock on to mechs with homing weapons, gauge their health, spot them on radar or map functions or even SEE them at a distance. This, coupled with the mech's relatively high speed and agility makes it tough to take them out to stop the ECM's jamming effect. The only other mech capable of equiping ECM is the Atlas, which turns it from a Mighty Glacier into a Demonic Spider thanks to the Atlas's large number of weapons and thick armor that are now under a cloaking field.
The regular splicers in BioShock games, specifically those armed with melee weapons and light guns.