This is very dependent on how you play the game of course, and the emotional attachment you have to each individual crew member, but the final scene to Mass Effect 2 is absolutely gut wrenching. There are many outcomes to the ending based on the decisions you make, by completing loyalty missions and how you play out the final mission itself. Characters live and die based on your actions, and even your characterized version of Commander Shepard can die.
I am not sure how many permutations of endings there are, but when my Commander Shepard jumped for the Normandy shuttle... my heart skipped a beat. "Was I a good commander?" "Does my crew trust me?" "Will the ship survive even if I do?" "Did this actually damage the Reapers?" All of these thoughts ran through my head in an instant. And then the unthinkable happened...
Commander Shepard slipped and fell.
Thankfully that was my second playthrough, but still... sad as hell.