Between Mass Effect, Mass Effect 2, and Dragon Age: Origins, I personally thought that Mass Effect 2 had the most replayability. The main reason is the gameplay. Beyond the story, ME 2 just plays amazingly, especially on the insanity difficulty. I've done a playthrough with almost every class (only class that I haven't beaten the game with yet is the Sentinel), and I've actually beaten the game more than once with the Vanguard class (my absolute favorite, especially on insanity).
The gameplay of Mass Effect and Dragon Age: Origins (PC) just didn't click with me like it did with ME 2 (and this is coming from someone who doesn't usually like shooters). Mass Effect 2, on the other hand, I can always replay, simply because of the combat. I think Bioware did a great job with the combat in ME 2, and I hope they don't stray far from it with ME 3.