Plaster Spider Splicers. Even after you KNOW they're alive, they still throw you off. It's really not a bad idea to shoot every statue in the head after that. Oh, and every dark spot on the ceiling, since they like hanging out up there too. They're silent except for the clanking of their claws, which sounds like just about every other ambient noise in Rapture. The worst part is when you hear their footsteps, and turn around just before they hit you. As soon as you lay eyes on them, they freeze. So you'll turn around to see a statue frozen in the exact moment before it was going to gut you. They're not even that threatening, but they WILL make you paranoid. I'll reiterate-They never let you see them move, and they sound like everything else.
Oh, and the Midwives from System Shock 2. Dead Space has nothing on that game.
Vagina doors from Prey, but they're not an enemy. When is a vagina ever the enemy? Please don't take that as a challenge to prove me wrong.
Facehuggers in AvP 2. Fast, tiny target that instakills. Much worse than poison headcrabs. Those things are just fat targets.
Anybody mention STALKER yet? The Snorks never bothered me too much, and Poltergeists weren't bad once you realized they couldn't really hurt you too much, but the Bloodsuckers...Were-Cthulhu with a Predator cloak. Jesus Christ, whoever thought up that gem deserves a medal, if they let him have it in whatever sanitarium he's in.