The Flood are the most retarded thing to ever be developed, ever. If Minecraft had The Flood in it, i would make it my life's goal to delete it forever. The people at Bungie who were responsible for the Flood level design need to bound and beaten for 23 hours every day for the next 10 years.
Oh, also every creature/pixel in Two Worlds...that game sucked.
The floods were pretty creepy first time I played Halo 1, but my most hated must be.. Cazadores from Fallout : new vegas.
The people who always jump in front of you and start singing and playing on their retarded little banjo things in AC: -Brotherhood. I always get desynchronized for stabbing like five of them in-a-row. xD But being serious I would have to say the final boss in Dead Island. I was standing by a pile of ammo behind a box and he just kept running into the box. Whenever I would run out of ammo my gun would get completely reloaded becuase I was beside the pile of ammo. I emptied my gun like 30 times until he finally died. xD And that really took a while. o.e MY FINGERS STARTED HURTING!!! D:
I'd have to say the The End from MGS3 (I know he's not a creature, so I'm just treating him as an enemy). He's pretty much the AI equivalent to a camper. He takes forever to kill and you need to use the SVD and thermal goggles (not really, but I recommend it). He's almost impossible and even I cheated to kill him on my first run of the game. Here's what I did, (there's 2 methods to kill him, one is the PS2 equivalent to the ever famous Konami Code that reveals his position.) I opened up my PS2 tray before going to pop in the game, went to the time settings on the console, and made it the year, like, I think 2017, I popped in the disk and the game had him die of old age. My suggestion is if you want his sniper rifle you either do the manly thing and fight him normally (I'll admit again that I pussied out and did the easy thing in this fight) or use the PS2 Konami Code to kill him.
EDIT: The PS2 Code is: Up, Up, Down, Down, Left, Right, Left, Right, Square, Triangle. (Do this on pause menu when executing the cheat.) And exit out the menu (if the code fails, try switching Square and Triangle, or use any combination you can think of using the main buttons (triangle, circle, square, and x).