3. Season 5: "Now or Never"
In one of the saddest finales ever, the doctors realize that the John Doe they're operating on is actually George (T.R. Knight), and we end up losing him. Meanwhile, Izzie's (Katherine Heigl) life is in the balance, and as the episode ends, it insinuates that George and Izzie could both be dead — although we all know how that turns out. Also important: The Post-It wedding.