Season 2, episode 27: "Losing My Religion"
In all onesty, season two is such a sad season. At the beginning of the finale episode, the interns stand together as a united front and each and every one of them take the blame for cutting Denny Duquette's LVAD wire. And Denny's fine . . . until he isn't, because you never know who is safe on this show. Denny dies and Izzie lays helplessly next to him until Alex carries her away, Snow Patrol's "Chasing Cars" playing softly in the background as Izzie confesses to cutting the wire, Meredith looks longingly at Derek, and Cristina holds Burke's injured hand. We aren't joking when we say that this might be one of the saddest scenes in television history.