The ending of MGS4 really prevented me from replaying it. Ditto for LA Noire.
ACR just about killed my love for the AC series. I also hated the yearly release deal, as it seemed each entry got worse. Heck i loved AC1, but ACR was just a chore. I have yet to get AC3 because of it.
Impossible(or just unfair) difficulty or required grinding(for RPGs) instantly kill my interest is games.
Total number of users on GameFAQS who I think should be thrown screaming from a helicopter:53.