A couple of mine just to kick this off:
1. Mosquito-bomber things. I have no idea of their official name (Vectorman) (Genesis/Mega Drive): Not because they're particularly tough, but because they're just so ANNOYING. They try to kamikaze you in swarms, infinitely respawn, are VERY hard to hit, and are usually placed just right to screw up an important jump. The only good thing about them is that you can sometimes take advantage of the infinite respawning to farm health from them.
2. Super Mutant Overlords (FO3): This one is pretty obvious. Enemies with so much health they can almost take a mini-nuke without dying. Oh, and they have some of the best Big Guns and Energy Weapons in the game. Oh, and the Tri-Beam Laser Rifle does double damage when equipped by them. Fun.
3. Riot Infected (Left 4 Dead 2): This guy is more annoying than most of the game's Special Infected since he's totally immune to damage from the front, meaning you have to single him out in a crowd, simultaneously defending yourself against a hundred other angry zombies who want to rip your face off, melee him to spin him around, and then shoot him in just the right spot. Good luck if you're on Expert or Realistic where the Common Infected do about 20 damage a hit.
