My most annoying are the black zombies in RE5.

I fealt racist when killing them and jsut couldnt do it.

Could you complete the game with this handicap?

haha nope i got past it eventually but did feal bad when my only black friend come around (NOTE i am in Australia so there isn't that many black people in relation to white, asian and indian).

The real handicap was the dualshock controller as it dfidn't feel like fun for me. I really wanted wii pointer as RE4 Wii  was fun.

Then a MOVE version come out so I got that. Was so mad haha.

the thin mans in XCOM are annoying as shit.

Space pirate from any metroid game. Kills the fun

I'm surprised that nobody mentioned Theseus from God of War 2, given the amount of users with a GoW avatar.

Instead of dying, when you defeat him he climbs on a building and begins to summons minotaurs, spikes and throw lightnings at you. You have to defeat the minotaurs several times to recover the magic you need to shoot at him with your bow.

And some retro stuff for those that like it:

This game is Return of the Invaders. See the three green enemies on top? Well, when you shoot at them if you don't hit them in the right pixel they deflect your bullets towards you at 10x speed.

This guy used to piss me off so much!  I'd be tracking his footprints or he'd be asleep and then I'd walk right up on him.  He'd see me before I saw him and shoot me.  He would get pissed at me for eating his bird.  He's hiding offscreen, talking shit.  If you don't find him fast enough, he regains energy through photosynthesis.  It always made me feel like a champion whenever I beat him fair and square.  Unfortunately, after that first playthrough, I I always cheated and used the thermal scope, microphone, and Patriot machine gun.  The fight went from taking an hour to taking five minutes.

hate them hate them