toughie......i'd have to say it's a three-way tie between the Elder Scrolls series, the Fallout series, and the Mass Effect series.
I have a large collection of games and these three are my favorites because of their replay value. I can always play another runthrough of any of these games and I never get sick of it. The first Mass Effect game was the first xbox game I ever played, and it's still one of my most played. Fallout 3 was the first game I bought when I got my own xbox, and I've logged over 150hrs onto a single save file just trying to find every single hidden treasure, bobblehead, and unique weapon. I've been playin the Elder Scrolls games ever since Morrowind, and they have some of the greatest replay values of any game series I've had the joy of playing. There are so many ways to build your character and the worlds they create are always completely immersive.
All in all, the best games for me are the ones that I can set aside for a month or two and pick up again on a whim and find myself as engrossed as I was the first time that I played. Fallout 3 and Fallout: New Vegas are particularly good at this, because they are honestly the only games I can say that I've played just to explore and listen to the in-game radio (some of my favorite songs of all time are on it). When you can pop a game into your computer/xbox/whatever just because you want to walk around in-game and listen to some tunes, it says alot for the game.