In RE4, something about the Regenerators when they first appeared had me seriously creeped out. It might have been something to do with their twitching and laughing as they followed you. Although they weren't remotely as creepy when I discovered that they can't withstand the Chicago Typewriter.
Definitely this for me as well! Especially the spiky ones.
The first play through, I stupidly sold the infrared scope. In the area after jumping down the garbage compactor(?), I used up all my ammo trying to kill the second one down there. Fortunately I had a rocket launcher. Unfortunately, the next area has a bunch of guys that wanted to kill me.
Oh, and same game- the village on professional mode with the chainsaw guy. I think I gave up after being decapitated around a dozen times. XP