Grim Fandango. I am a fan of the old Lucas Arts adventures. After hearing a lot of praise for Grim Fandango, I got it and was in for a shock. The shift to 3D meant that all of a sudden, the controls were keyboard only. I tried to get used to it, but after an hour of running into walls thanks to the retarded early Resident Evil style control scheme I gave up. I repeated that process of trying to get into the game and eventually giving up for about 2 more times. Then I left the game gathering dust for about a year.
When I played it for the last time, I promised myself to not give up. And eventually, as humans do, one gets used to anything. It was worth it. It's the best Lucas Arts adventure I ever played, beating even Day of the Tentacle.
Another game coming to mind is the first Gothic. Obnoxious combat control scheme, but once you accept it for what it is, you get into the rhythm of the game, and it was one of the best RPG experiences I ever had. It evokes real nostalgia...