A game referencing many tropes and classics itself by design, Scott Pilgrim vs. The World - The Game features hordes of flying bats that intentionally spawn when least convenient. This is most evident during tricky platforming sequences. Hilariously lampshaded, as the bats are called G. D. Bats.
Pitfall II was a 2D game which had bats that simply provided a moving obstacle. The bats would fly across the screen and you had to time Pitfall Harry so he passed under the bat while its wings were flapping up rather than down. (Pitfall Harry couldn't just crawl or stoop, nossir!) Unfortunately this was used for about 15 floors in a row and got old REAL fast.
Tomb Raider has bats, rats, baby dinosaurs, big burly gunmen, scorpions... each game has at least one pain to deal with.
The Last Revelation takes this trope literally. Bats are everywhere, even when the apocalypse is descending upon Egypt and you've started fighting giant scorpions.
The bats from Captain Comic 2 were dangerous and annoying, and they showed their worst in a particular cavern in the Arctic World, which was nigh impossible to traverse without losing half of your health to them.
The decidedly unpleasant Fallen enemies in Devil May Cry 3. Not only do they have a (respawning) shield in the form of their wings, which you must break before actually dealing damage, a fair amount of health, and strong attacks with a variable-length short sword, they also can phase through walls and tend to stay in the air. Because the game rewards based on combo level, and your combo ability is limited in the air, this means that after going through all the trouble to kill them you receive almost no reward.
In the same game, you have the Dullahans, which are floating armor invincible except for a certain move and an Achilles' Heel on the back. Not only are they almost fast enough to keep up with Dante or Vergil trying to circle around them, they can also turn while under attack, an upward thrust attack makes the vertical route difficult and they usually appear in tight quarters. On higher difficulties they never die in one hit.
There also are the Soul Eaters, which do not appear unless Dante or Vergil has his back to them. Their dash attacks carry them in and out of the camera's view. They also do not die in one hit. And if they hit you, they drain your Devil Trigger. The best way to fight them is to keep your back turned until they solidify, wait for them to move (which prevents them disappearing), and then turn around and gun them to pieces. Of course, on higher difficulties, they become especially annoying... Especially on Dante Must Die, where they activate their Devil Trigger and gain annoying amounts of vitality.
While Hell Lusts stay on the ground and can be combated like most of their cousins, they have an annoying uppercut which can come out faster than anything Dante or Vergil can do. Also, it is prefixed by a dash which is usually a feint, making it very difficult to tell when they're gonna pull it off. Any self-proclaimed "true fan" who doesn't have sharp words about the "Lustercut" isn't as hardcore as he'd want you to believe. Furthermore, they are apparently enough of a Determinator demon-type that they can hit with it even when dead. Behold.
Devil May Cry 4 brings us the Gladius demons, which transform between a sword and a reptile form, and both fly. They love striking you out of combos, and they never come alone.
DMC4 also has the particularly annoying Chimera enemies. Alone, they're not a problem, but they have the ability to latch on to other enemies. They're still not particularly dangerous, but they increase the health of whatever enemy they latch onto, and they can attack while their host is flinching, which is hell on your style meter. They can graduate to Demonic Spiders when possessing tougher enemies, like Assaults.
Let's not forget the Mephistos. They're immune to conventional damage AND they can fly through walls and floors, making attacking them a royal pain in the ass. They can literally attack you FROM ANYWHERE. Then there's the Faust...
The first Devil May Cry game presents this trope with the Plasma enemies. They literally are bats, split into and spawn more of itself (restoring its HP to full), shoot light beams from their eyes in both horizontal and vertical paths, render Alastor ineffective, and in Dante Must Die mode are seemingly put there to screw the player over (or force them to use Ifrit, whichever is worse).
Dm C Devil May Cry, despite being considered easier than its predecessor games, have quite a few examples:
Blue and red enemies at the same time. On their own, each is already annoying as blue enemies can only be hurt by Angel weapons while red enemies can only be hurt by Demon weapons. Facing both of them at the same time means that either you have to constantly switch weapons to stagger them both or focus on while while keeping an eye out of the other which will be immune to your current weapon.
Shielded Pathos. Their attacks are aimed straight at you, and their shields means that you have to spend some effort to strip their defense before you can whale on them. The good news is that their health is miserably low, the bad news is that you'll never see them alone.
Harpies. Until you get a shotgun, trying to focus fire on these flyers is a chore due to their agility, and like Shielded Pathos, they will swarm at you.
The satyrs in God of War are a source of eternal frustration for many a player, thanks to their seemingly immaculate ability to dance away and smack you whenever you dare to contemplate hitting them.
Wraiths and Harpies, especially after they've learned that Firebomb attack. Their death animations are too perfect. It's like the designers came up with that first, then said "What attacks can we give them that will make the player want to do just that to them?"
In God of War 2 there is a level where the player must climb a long chain to get to the top of the level. Along the way there is an endless supply of Bats that you can not attack from the rope and can throw you from the rope.
The goddamned jetpack laser soldiers in the final areas of the game especially stand out. You pretty much have to use scrolls on them, because no other weapon will kill them fast enough to keep them from killing you. And their lasers do the most damage of virtually any enemy attack in the game, and they can be hard to avoid especially in corridors.
Slicer badniks in Sonic the Hedgehog 2 are horrid examples of this trope; they have blades on their arms that they can throw, but while doing so renders them mostly harmless, the blades themselves have an uncanny homing ability that makes it nearly impossible to kill or get past them without getting hit. Worse yet, they always seem to appear at crucial jumps, making them an even worse threat than usual.
Also Flasher, firefly-type badnik, possibly the closest thing in Sonic 2 to actual bats, had the same tendency to be placed right in the middle of crucial jumps, and ALWAYS turn on their flashing light invulnerability the instant Sonic tries to attack them.
The bomb types in the 2D games have an annoying tendency of timing their explosions in such a way as to be near unavoidable.
All three badniks from Metropolis Zone (the aforementioned Slicers, exploding Asterons and the always-awkwardly-placed Shellcrackers with-giant-fists) stand out as being pretty much the only badniks in a classic Sonic game that actively make their level hard, as opposed to, say, environmental hazards (which Metropolis also has plenty of as well, being the Scrappy Level that it is).
The Artificial Chaos enemies in Sonic Adventure 2 are incredibly hard to hit (because the Homing Attack has terrible lock-on, and in the mechs, you'll probably accidentally shoot a Dynamite Pack and get sucked into space), and they can stretch their arms and attack from a distance. Then, in Shadow'sveryowngame, you are expected to kill forty of them. And they make the Collect 100 Rings for A Rank stuff for all the emblems tedious, and to some, impossible.
The little known spinoff Tails' Adventure on the Game Gear featured honest to God robotic bats in cave levels, whose whole purpose in existence was to knock you off ledges and disrupt precision platforming.
The pumpkin ghosts in Hang Castle and Mystic Mansion stages in Sonic Heroes. They show up at exactly the right moment to knock you off unless you're expecting them, and a hit from them counts as a hit from a normal enemy, plus they move fast and even if you kill them they never drop level up orbs. And the way they laugh at you when they damage you. Ugh.
Sonic the Hedgehog CD had the Hotaru lightning bug Badniks. They aren't much of a problem until the final act of Metallic Madness where you were forced to fight them in a small enclosed area. Most of the time the damn things would soar high into the air, completely unreachable. The window of time in which you can hit them is pretty brief, and on top of that, they fire lasers while you aimlessly jump about hoping for that one perfectly timed hit. If that doesn't qualify for a Goddamned Bat then I don't know what does.
Prince of Persia: The Sands of Time has swarms of bats that tend to show up when you're perched on a ledge hundreds of feet above ground. A couple of unlucky hits will have you falling. There are also vultures that attack you while you're climbing ledges, and at some points they literally hang around in the area and do not attack unless you start climbing or balancing on a precarious ledge.
The archers in Prince of Persia: The Two Thrones. While not small, and not flying, they are weak (they go down with one quick-kill and have very little fight in them), ubiquitous and very annoying. Their arrows, which they'll launch across entire rooms, don't do much damage, but they stop whatever action the prince is doing, including attacks and especially combo moves. They also make you instantly fall to your doom if you get hit in the air.
The beggars, drunks, lepers, and crazy people in Assassin's Creed I are annoying as heck; the former follow you around, nattering your ears for money and getting in your way right when you're trying to stealthily assassinate that oblivious guard up ahead. The latter simply smack you violently and shove you into walls, guards, and off ledges. It quickly becomes an exercise in patience to not simply draw your sword and start satisfying that Videogame Cruelty Potential.
The minstrels in the second game are similarly annoying, but this time you can throw money to distract them, bump into them to break their instruments, pickpocket them... it's a lot easier to get rid of them, in short. Or, since this time around the guards don't mind you getting into a fist fight so long as you don't draw your weapon, you can pummel their brains into the pavement.
Archers. Up close, when they drop their bows for melee weapons, they are just like any other guard. It is when you set them off while they are afar that they become problems, firing their unblockable arrows to open you up for attacks from other guards or making you fall in mid-climb.
Agiles from 2 onwards can run you down even when you're in a full sprint. They are very weak in a stand-up fight, but if for whatever reason you cannot mow them down in combat, you will know pain.
Any enemy that can grab, before you get grab breaking back.
The rooftop riflemen from Revelations. Really squishy, slow to reload, but each shot deals a tremendous amount of damage (especially on low levels) and the fuckers are EVERYWHERE. As if that wasn't enough, most Assassin Dens in the city are surrounded by bunker towers filled with these riflemen who for some reason gain the uncanny ability to see and attack Ezio from unrealistic distances, making the often already troublesome search for the captured den's Templar leader even worse.
In III, Jägers. They combine every trick of the other mooks into one tough to kill Elite Mook. Attack aggressively? They parry you. Chain killing? Hope they're disarmed or in front of a wall or ledge, cause otherwise in isn't happening. Try to counter or throw them? Denied. Try to stun them? You get bitchslapped. Want to shoot them? Guess what, they've got enough health to take one shot, when you have a maximum of four before you need to reload, a several second process that's practically impossible to do in a fight. Now, there are still a lot of ways to kill them (A lucky shot to the back, using them as Human Shields, double or triple counters, etc.), but just about the only way to kill them yourself is to disarm and then combo them, and it only takes a single attack from another mook and they'll have the chance to pick up their sword or any sword or musket laying nearby, bringing you back to square one. Either that, or a gun/bow counter that will be instant death, but can still be interrupted, and you only have so many bullets and arrows. Furthermore, they can shoot with little warning, mount a horse from which they can shoot you, can catch up to you like the Agiles mentioned above, and can free-run to follow you on the rooftops. They're annoying enough when you fail to assassinate the Jäger that acts as a forts commander, but when your notoriety reaches three, these sons of bitches spawn everywhere and will patrol both the streets and the alleys, making it damn near impossible to move around without triggering a tough chase or a long, drawn out fight.
The hawks from Ninja Gaiden. A lot of people will tell you they're at least as bad as Castlevania's flying Medusa heads. A lot.
The game also has actual bats. Those are easy whenever you see them coming, but there's a crapton of Bottomless Pits where a bat spawns while you're right at the edge of it, knocking you down to an instant death. You'll basically need to stop for a bat check before every unknown jump.
As well as featuring bats, the Xbox Ninja Gaiden [Black] includes ghost fish enemies towards the end of the game. They attack in large numbers and can only be safely defeated with a continuous flail combo - pause for a moment to pick up the blue health orbs they leave behind, and they'll be on you in an instant.
And the grenade spamming dogs in NG II.
The weird glowing slugs in Battle of Olympus for the NES.
There's also the Angry Sun, which flies erratically all around the screen. Fortunately, it only appears twice in the entire game, and can be killed for good for the rest of the level provided you have the ultra-useful Hammer Suit or hit it with a Koopa shell.
Super Mario Bros. 2 had Phanto. He really didn't like you taking keys, and was the thing nightmares were made of.
Super Mario Sunshine, has Boos, Smolderin' Stus, Cataquacks, Electro-koopas, Klambers, CooCoos, Seedy Pods, Swipin' Stus, Wind Duppies...
Everything in Super Mario Land is a pain in the arse by world three. Especially those flying head things that always bounce around on a series of platforms that you have to jump onto. Also, in any Mario game, Spiders manage to be a pain whenever they appear.
Super Mario Galaxy has literal Goddamned Bats in a few levels. Usually, they just bump into you and are a pain in the ass to kill. But put them in the Slippy-Slidey Ice World and you get Bats that freeze you solid, and can only be killed by the temporary power-up that is difficult to aim at stationary objects, let alone flying ones. What really makes them irritating is that if they score hit, they actually laugh at you.
Bloopers/Bloobers in Mario 1 and Lost Levels. Especially when they decided to pop up in the middle of an overground level for no reason. Squids in mid-air!
Lakitu. The bastards fly around, always just out of reach, while dropping spikes into the player. Peach help anyone on the receiving end of a Lakitu that drops independent enemies.
The Final Boss of Super Contra (arcade) periodically spawns literal bats.
The bats in the Dungaga mines and Grodol caverns in Eternal Daughter. As if the floating carnivorous strawberries, summoner rabbits, spiked slimes, sneaky earth elementals and rib-launching skeletons weren't bad enough, there's also the Goddamned Bats popping up at random, aiming to disrupt you whenever you're doing anything remotely requiring precision.
La-Mulana has a disgusting variety of enemies which fly or jump around erratically, and often through walls as well. The bats (two varieties, in fact; one of which moves faster and is more annoying) are especially noteworthy because they fly around in a completely random pattern, with no warning as to where they're going to turn next, and fly through walls as if they aren't there (and are invisible in water); the remake makes you immune to them if you get the Scripture. And then there are the magical staff-wielding monkeys, the singing witches and the Frickin' Laser Beams-spamming blue imps. All can flood the screen with wall-penetrating projectiles in a matter of moments, and the monkeys are invincible except when firing, while the witches and imps fly around randomly in a similar fashion to the bats.
The developers even acknowledge how annoying the bats are in the remake; there are several references to "bat curry",
Let's not forget surprise fish!
Large part of the abundance of annoying enemies are because of game mechanics too. Character is sent flying backwards every time after getting hit, often to another screen, which, combined with Respawning Enemies, can be quite an annoyance. However, once you boost your maximum health a bit and get some defensive items, regular enemies remain annoying as hell but will rarely actually kill you. That is the province of bosses.
Impossamole has origami birds, ninja rats, and acid-raining clouds in the Orient level, as well as UFOS that can pass through walls and invincible the pirate ghosts in the Bermuda Triangle (the Amiga/C64 version also featured literal bats in the Klondike Mine, many of which were invincible, some unavoidable), and Action Bomb enemies in the form of walking dynamite sticks. In the TG16 version, they can also knock you backwards (although you have Mercy Invincibility), interfering with already difficult platform jumping and sometimes causing you to miss one of the scrolls. In both versions, they often endlessly spawn from Mook Maker doorways. In fact they usually respawn when you return to an area, and you often can't tell whether you're going to land on one when falling.
Some egregious Scrappy Levels in the TG16 version: Bermuda Triangle Level 2: The "Hallway Of Doom", where you have indestructible falling blocks that can be kicked out of the way, but bounce back and forth, along with Mook Makers churning out unkillable ghost pirates and barrels, living cannonballs, and in a really cruel item placement case, a health powerup blocked by a falling block which you can't jump over, and will take damage kicking it out of the way, which can render your efforts to get it in vain. At the end of the same level, you have to walk under a series of falling blocks to get the last scroll, then swim back through a field of randomly moving water mines. In Orient Level 2, the Ninja Mice/rats are more agile and have projectile attacks, making you a sitting duck without a ranged weapon. AND you have to fight through a swarm of them, dodge rain from invincible killer clouds, and negotiate platform jumps at the same time JUST to get one of the scrolls. This where they cross the line to become Demonic Spiders. In the same level, you also have to jump over Spikes of Doom pits with falling boulders conveniently placed over them (no Mercy Invincibility to spikes). And the underwater sections of the Amazon (luckily Monty doesn't have drowning skills, unlike Sonic). Since you can't attack underwater, all such enemies are effectively invincible.
The flying heads in Prince of Persia 2: The Shadow and the Flame were very quick attackers who liked to push you off a platform and then fly down to the lower platform and continue their attack. Worse, you've lost your sword when you first meet them, and can only fight them with a wimpy little dagger, which makes it trickier to hit them, and not hitting a head means getting hit by a head, which could cost you as many as three units of health. The game gives you a real sword after a couple of levels, and right after that makes you fight 9 heads in a row.
Abe's Oddysee has Goddamned Bats. They are the only enemy that flies, can't be killed, instakill Abe if he touches them and while they do follow predetermined patterns, it's impossible to predict what the pattern will be without watching for a few seconds first — a luxury the player doesn't always have. Unlike the other enemies in the game, they have no AI whatsoever and so can't be tricked, possessed, distracted or otherwise moved out of the way. They're just there, fluttering around the screen, waiting patiently to kill you yet again. The game knows full well players will hate them: in the first screen that features a bat, the player is likely to ignore it as background detail, and read the more obvious firefly hint instead. This requires holding down 'Chant' and waiting while the fireflies form into words. "WATCH... OUT... FOR... THAT... BAT" - upon which the bat flies into you and you promptly die.
Legacy of Kain: Soul Reaver has its own Goddamned Bat in the FIRST BOSS LEVEL. On your way to defeat Melchiah, you meet his brood that have the same "abilities" as he. What's that mean? Simple: they heal REALLY quickly from just about any wounds you inflict, and if they are killed, but the soul not taken? They come back just as quickly. Oh, and the best part? They can dig underground and pop out at the worst possible time, thus making them invicible while you try to dodge their attack (and they almost always hit). Doesn't help that lethal weapons are kinda hard to come by in that level....
Lego Star Wars II: The Original Trilogy:: Episode V: The Empire Strikes Back:: Chapter 4: Dagobah — the only stage to have Lego bats. And they are very annoying. Luke can kill them somewhat easily at the start of the stage with a blaster, but midway through the stage he starts his Jedi Training, and for some reason it's really darned hard to kill bats with a lightsaber.
It's hard to go anywhere in Beyond Good & Evil without encountering huge swarms of Goddamned Rats. Although a single kick or Gyro-Disk will kill them, they often come in such enormously massive numbers, at least one of them will manage to nibble Jade's health down before you're done with them all. A few areas also have large numbers of slugs, who will OM NOM NOM the heck out of your legs if you let them.
Yakuza throws a random encounter at you almost every block. It wouldn't be so bad except they're hard to pick out in the game's massive crowds, they tend to approach you when you're right on top of them, and you don't usually have time to avoid them. If you're sharp, you do run notably faster than them, so getting away can be easy on occasion. Yakuza 2 seems to have toned down the random attack rate.
Also, every single non-boss enemy in the game continuously spawned (except the Pod Plant). Zombies burst from the ground, Evil Dolls hacked their way out of boxes, Mummies emerged from sarcophagi... In fact, nearly every enemy in the game is a Goddamned Bat.
The Little Big Adventure games have Goddamned Bats and Goddamned Fireflies. Being small and quick, they are incredibly hard to kill, and while they don't appear in swarms, they have a tendency to fly over water or lava — if you are using a jetpack to fly over these, and get hit by such creature, you are dead.
Fester's Quest had this very annoying green sphere that would forkbomb on every hit, and the longer you took to kill each semi-overlapping new sphere, the more likely each one had of forking again. Worse yet, the game had a nasty feature in the form of negative powerups. So at the end when you had killed them all off, usually you had to avoid the huge pile of treasure completely.
The Pygmy Bulborbs in Pikmin 2, and their close cousins the Water Dumple. While they'll die fairly quickly (and a single WHOOMP from a Purple Pikmin will kill them), they occur in large numbers, and the likelihood that at least one of them will manage to munch a 'min is high. Unfortunately, they tend to serve as only a distraction for a much larger, more dangerous enemy...
The male sheargrubs. In Pikmin 1, these things are invulnerable while they eat your Pikmin. Due to this, they'll always kill at least one Pikmin, unless if you throw a Pikmin directly on top of it, or punch them to death.
Funny enough, the NES version of Dragon's Lair subverts this, as every enemy kills you with one hit except for the bats, which only take off some health and won't even make you flinch.
Turkey Commandos from MapleStory. They spawn alongside weaker enemies in the starting areas of the game; they move faster than a low-leveled player normally does; their touch attack deals more damage than the local enemies; they have a laser attack that can hit you from off-screen; they can jump; they have high avoidability, making them hard to hit (especially at low levels). Luckily, they only appear during the Thanksgiving events.
And also, the enemies in the Jump Quests, MapleStory's answer to That One Level. They're invincible and their only purpose is to knock you back down to ground level, forcing you to restart. God help you if you accidentally try to hit one that flies, since it'll follow you around for a good five minutes. Note that all enemies in the game move around in a random pattern until hit (at which point they follow their attacker), save for the enemies that can't move at all. Monsters that fly move in an even more random pattern because they move in two dimensions instead of one.
In Custom Battler Bomberman, you'll start hating those red balls that come out of the teleporters in Zone G. Why? well, let's start listing them:
If the teleporter's tile gets hit with a bomb's explosion (even if it's not your bomb), it spawns a ball.
In some levels, security systems spawn MORE of those balls if tripped. Scrappy Level, anyone?
If even ONE ball is in the level, it has to be destroyed before you can use the teleporter, even if the "mission" requirements are met.
All of the level timers going on do not wait for you to clear them out.
And let's not forget they can always go faster than you. Always. well, unless you have one specific ability which you'll probably have used a lot by the time your reach Zone G thanks to Ridiculously Hard Levels (some of which teeter on being a Luck-Based Mission due to block placement and strict timers), but even then, faster than your running speed.
The flying and armor Gaudis in Cave Story like to hang around ledges and lob projectiles at you, which are liable to level down a weapon you'll want for taking down That One Boss (whose Boss Room contains a whole bunch of them). Earlier on, the Sand Zone has flying projectile-spewers in the form of Crows carrying Skullheads, two enemies more annoying together than when separated. And there are the Butes, who help put the "hell" in the Bonus Level Of Hell.
Not to mention actual bats. Sure, they go down in one hit, but they can make maneuvering more of a crapshoot, especially in the firstBonus Level Of Hell.
The Troopers in Metal Arms: Glitch in the System dodge your shots, move around quickly, have many hit points, powerful attacks, and can fly.
Guards and Zombiebots have hugely powerful melee; it deals knockback, and drains your health in seconds. Furthermore, when you encounter them, good weapons are either rare, requiring multiple shots to kill them.
Entirely avoided in Shadow of the Colossus, which features no random encounters whatsoever - the player is a lonely, lonely man in a lonely, lonely landscape. There's exactly one very short cave with bats, but killing them is about as pointless as shooting at trees.
Heavily lampshaded in the opening sequence: something eerily similar to the main enemies from ICO appear for a split second, but are instantly killed by Wander's sword. They never bother him again (not when he's conscious, at least) and neither does anything else apart from the titular colossi.
In Thexder, both the 1985 original and the 1995 remake, a great many enemies fall into this category - which is quite impressive considering that the titular character's laser has auto-targeting.
Heart of Darkness has a variety of enemies like this, though it's hard to tell if they're just Goddamned Bats, or outright Demonic Spiders. There's literal spider enemies that appear on climbable walls (who jump around erratically, dodge your shots almost constantly, and create acid globs that can make you lose your grip on a wall if you touch one), flying bat-like enemies who can throw fireballs in all eight cardinal directions, and worms that pop out from climbable walls and can snatch you in a fraction of a second. In the case of the spider and bat enemies, they sometimes have the gall to survive an abnormal amount of shots from either your blaster or your magic attack, depending on which level you're in. Even the normal shadow enemies have this trait, which may or may not be randomized amounts of health for each individual enemy.
Rastan has some levels with Goddamned Bats that are hard to hit, suck out your life, and throw off the timing to the rope swing challenges. Very, very annoying.
The unlicensed Famicom game Thunder Warrior is riddled with bats, especially literal bats, as well as WallMasters, exacerbated by Bottomless Pits, slippery controls, and the hero's hard-to-aim projectile attack.
Home Alone 2 has literal bats too which very often knock the player off of tiny platforms. In addition, rats are almost as big nuisance.
First Wizards and Warriors game has many Goddamned Bats, including literal ones.
Kid Icarus: There's the Reapers and their Reapettes, the Mono-eyes and other flying enemies, and the jumping crabs, which are a major pain in stage 1-3.
The bats in StarTropics. In the first game, they were common enemies that flew in a pattern, took one hit to kill, and would stop every few seconds. In the second game, they don't appear until Chapter 7, but they take two hits to kill, fly much faster, have no set pattern that they fly in, and don't stand still. The problem is amplified because the game lacks Mercy Invincibility, so if they corner you they could wipe away your hearts in a few seconds. Plus they're always in groups of at least three.
The bats in Beyond Oasis for the Genesis, first appearing in the fifth dungeon, are textbook examples. They're extremely difficult to hit, come in groups, and do enough damage to kill you in no time.
Virus detectors in Prototype can see through Alex's disguise, making sneaking difficult until you learn how to sabotage them. Then the un-sabotageable UAVs appear to take up the slack. For extra "fun", attacking these even with guns will still give Alex away. Plus Strike Teams usually come with at least two. At least they can't directly attack.
The whirlwinds inspired controller-flinging fits in Toejam & Earl. There's nothing quite like a hazard that spawns without warning, scoops you up in its inescapable embrace, and drops you anywhere it can reach, including over pits that will drop you back down to the previous level. Even worse, you have to sit and watch for 10 seconds or so while the tornado moves around randomly deciding where to dump you.
The hula dancers, who pose no direct threat but will randomly cause Toejam or Earl to stop what they're doing dance in place, even if they're surrounded by bogeymen.
The goddamned blockers from Wet, which have to be killed via manually-aimed head shot, or explosive, or melee, because they'll stand there and block your off-hand gun if you auto-target them. And to top things off, these guys do very nasty damage with their melee attacks. The icehouse arena level from stage 8 is when these guys first appear, and it's part of the reason the level is considered That One Level.
Dynasty Warriors 6: Empires features various kinds of goddamn tigers and wolves, which move around in highly erratic patterns and can apparently only be killed by hitting one specific point in the middle of their spine. Yes, you can be whaling away on what appears to be their face and nothing will happen. Some breeds can also shoot lightning or freeze you in ice, both of which will temporarily paralyze you - this usually isn't fatal to the player, but the same cannot be said for any hapless civilian you may happen to be leading on an Escort Mission...
Related to the above, Samurai Warriors brought us the ninja vareity of enemies. Not just your traditional smokebomb and sword ninjas either—no, you had to deal with the Wind Ninja, Strike Ninja, Sky Ninja, and Fire Ninja, too. None of those were Boss in Mook Clothing bad, but they all had one thing in common: the ability to knock you out of combos and off your feet. Wind Ninjas move quickly and unpredictably, but at least have the decency to telegraph their attacks while wearing the single most absurd bit of headwear seen on Hack And Slash blade fodder. Strike Ninjas—better known as frickin' sumo wrestlers— are slow, but absorb hits like they were nothing, and on top of unblockable attacks, also could throw your character a good distance. Sky Ninjas, contrary to their name, don't use aerial attacks. Instead, they just tunnel into the ground, chase after you, and pop out at inconvenient times, usually knocking your character down. On top of that, only one type of attack affected them at all while they were underground, a usually-weak Ground Pound attack that more often than not had a lot of recovery time. Finally, there are Fire Ninjas, which are really just well-armored guys carrying a backpack full of big black bombs. Unlike the other 'ninja' mentioned, they don't flash, make noises, or wade after you like a leather-wrapped meatloaf with feet. No, they just quietly light their bombs and chuck them with depressing regularity at you. Ranged unblockable area of effect attack that usually hacks off a good chunk of your life in flame damage. Bloody ninjas.
Related, at least in the first game, are rifle squads...unblockable targeted ranged attack, in a game that let you deflect arrows, rendering all your practice with the skill moot. One character, Magoichi Saika, sometimes became a nightmare to play against on harder difficulties because of the fact that it was pretty much impossible to counter his bullets, but these being rifle bullets and this being medieval Japan, they were Truth in TelevisionGame Breakers.
Dynasty Warriors: Gundam, being made by Koei as the above games, gives us rocket-equipped grunts. Woe to you if the computer assigns suits such as the Rick Dom, Rick Dias, or Ball to the enemy. In a game where enemies were often reluctant to wade into melee with you, the AI mooks' tendency to hold back and fire at you was merely an annoyance when beam rifles and machine guns were plinking off your armor, but rockets delivered knockback—even the most powerful Mobile Suit was liable to be knocked down by a barrage of rocket shots. Being assigned these enemies as mooks could make entire armies into a horde of Goddamned Suits.
In the first Ratchet & Clank game, Planet Orxon gives us an example of combining goddamn bats with Demonic Spiders. Orxon is overrun by Land Lobsters, very tough, very mean enemies that come in packs and love to surround you and kill you dead. Fortunatly, the Land Lobsters tend to sleep alot, and will likely be sleeping when you encounter them. Enter the (goddamn) Screamers, who will fly in the air and screech obnoxiously, waking up and attracting nearby Lobsters. Screamers can be taken out with one hit, but if you miss or accidentally hit a Lobster, well...
In the second game, once you got used to killing the YETIs they stopped being Demonic Spiders and instead turned into these. They do pose a significant threat, and are better classified as Demonic Spiders, but since you have to face about three thousand of these to get all the crystals in their area, one will inevitably find a way to kill them fairly easily. The problem then stops being staying alive and turns into avoiding situations where you're surrounded and not running out of ammo, both of which are rather difficult since every time you get a crystal some of them will pop up around you (or some spawning points will open up and throw around ten of them at you each, one at a time), surrounding you in a split-second; and since they have rather high health, which, combined with the whole three thousand of them thing, means you're going to run out of ammo very frequently. They can also tend to be annoying to hit since their attack quickly moves them towards you and then back a significant distance away, and they counterattack anything.
The Sir Slush enemies from Banjo-Kazooie. They are snowmen who throw snowballs at you, and the only way to kill them is to Beak Bomb them on their top hats; it is very easy to miss them. It gets worse when you're playing as the walrus, who can't defend himself at all, and Sir Slushes' aim tend to be dead-on.
The goddamned snipers from the Dick Tracy NES game. They appear on top of buildings and shoot at you whenever you hit the streets and drive to where you want to go on the map, and very often, they'll hit, draining your precious energy away, making it all but impossible to even complete the first major case without dying. The only way to kill these guys is to get out of the car and pick each of them off, which slows things down and makes you just as vulnerable to getting shot as when you're in the car. To make things worse, the only way to restore your health is by collecting hearts, which do not restore your life meter, but are actually First Aid, which you use by hitting Select while the item BEFORE the First Aid is selected, holding it down and hitting B to restore your health (which few players would know how to do back then). And to make matters worse, one life is all you get, and there are NO FUCKING CONTINUES.
One of the earliest examples has to be the bat from Adventure, who would randomly move objects around the game world just to mess with you.
The Rayman games have several different instances of this. Rayman 1's Antitoons come in a variety of different types—each with their own unique abilities or a combination of several— and are aggravating whether they're alone or in swarms, mostly because they're hard to aim at and impossible to tell apart just by looking at them. Rayman 2 has actual bats, puffs of smoke/ash that fly into you, miniature critter-sized spiders and crabs that can somehow damage you on contact despite being smaller than your shoe, as well as countless other examples. But the most notorious and recognized ones among the series are probably the Goddamned Zombie Chickens, which make appearances in both Rayman 2 and Rayman 3.
The basic ghosts from The Haunted Mansion attack in swarms, usually when there are more powerful enemies around, and are so small you often can't see them until they are right on top of you.
Quattro Adventure collection has Linus Spacehead which has numerous enemies that kick you back, but won't hurt. Some of them are also Ledge Bats. One of the enemies in the second level carries you several sections backwards so you have to gain the lost ground again.
Inverted in Dark Siders, where the first dungeon has bat enemies that aren't particularly fast, powerful, or difficult to hit, and can be killed instantly with a grapple attack. You can even grapple from one bat to the next in mid-air, and each one gives you a health boost!
inFAMOUS has the obnoxious little scorpion anklebiters in the Warren. They pop out of random crates in groups of four and start nipping at your heels, then skitter around the nearest corner as soon as you fight back. They're more annoyance than hindrance (a shockwave will usually make them all pop), except when they're accompanied by their Mook Maker, who will use the distraction they create to pick you off with a rocket launcher.
Gods Eater Burst has a few enemies that might qualify, but among the most widespread are the Zygotes, floating enemies that aren't particularly difficult to kill by mid-game, but often appear alongside stronger enemies and like to inflict status effects or generally distract you from the main threats.
In the movie Labyrinth, fairies left Sarah once bitten (literally), twice shy. In the Famicom game of the film, fairies are even more annoying, as they like to show up in swarms, move quickly, ignore walls and try to avoid line of sight. At least they're weak.
No More Heroes and its sequel feature melee combat... for the most part. Then we have the gunmen. They like comboing you with their bullets, interrupting your attacks, stunning you, knocking you down, attacking among groups, runnning away, and letting the enemy you were attacking beat you down if you're not careful enough. It should be mentioned that gunmen are the ONLY ENEMIES IN THE GAMES that focus on indirect combat and keeping distance. They're worse in the second game thanks to the ecstacy gague. You have it 100% and you're gonna unleash it soon? A gunman shoots you with four bullets, the gague is now completely empty. They're so bad that they're the only regular enemies in the game with a different icon than every other enemy.
Pretty much all of the small monsters in the Monster Hunter series. While they cause virtually no damage compared to the large monsters, they can still interrupt your actions and knock you around, which can leave you at the mercy of the large monster you're trying to deal with. They also tend to respawn repeatedly even if you kill them off.