Dead Space was the first (and sadly only) game that has ever made me legitimately freaked out enough that I had to take breaks in playing it. I played plenty of horror games before, and after obviously, but none of them made me feel as uncomfortable and legit frightened as Dead Space did.
There were a few games that came before it that unsettled me a bit - REmake with the hall in the east wing where zombies burst through the windows and pour through was a very unexpected and fun way to be startled when I first went through it, but the Resident Evil games have never really scared me, even when I played them as a kid, so it was more of a simple jump scare startle then anything else.
-Insert witty signature here-