Mafia, I think. Must have played through it entirely 5 times, probably started and stopped at other times too. It's fucking brilliant - shame it got tagged with the "GTA clone" tag. By morons, I might add.
I think I probably devoted most man hours to Oblivion though, since I have been through almost every quest at least once.
The only ones I haven't done are The Grey Prince, and The Collector.
Even though I haven't played it in at least a year and a half, it bothers me enough that I've never done those two xD
I don't know why I've never done the first, and the second is just so massive that I can't keep on it without getting distracted.