For me, it was Resident Evil 5.
I loved the series from the beginning, with 2 being my favorite, and 4 and REmake not far behind.
I bought RE5, played it for maybe 10 minutes...and never played it again. It was just so.....NOT Resident Evil. Sure, 4 was more action-oriented, but at least it still had survival horror aspects. RE5 was just a straight-up action game, and a mediocre one at that, with too much of a focus on the multiplayer teamwork aspect.
at Bioshock Infinite mentioned in here. I’m just finishing up another playthrough and I just love it so freaking much. Probably my favorite of the series, but the first Bioshock comes close.