The Fallout and Elder Scrolls series are big ones.
The Witcher series, though Witcher 2 at least has a steep learning curve I found.
The Deus Ex games, particularly the latest Human Revolution.
The Mass Effect trilogy, as well as Dragon Age.
The Far Cry series.
Dishonored, quite good if your a fan of Victorian era Steampunk and stealth.
Borderlands, though its much mroe focused on shooting than the RPG elements.