5. Burke's cover-up (Seasons 2 & 3) Burke gets shot outside the hospital, and the talented Seattle Grace surgeons patch him up. Soon after the trauma, his hand starts spazzing, which is very bad news for a chief cardiothoracic surgeon. So, with his reputation at stake, he tries to hide it — and, against her better judgment, Cristina helps. Both of them blithely ignore how dangerous their little conspiracy is to the patients they operate on. 4. Denny's death (Season 2) The budding romance between Izzie and Denny is fun to watch, and after his transplant we expect them to play Dirty Scrabble for years to come. But then he dies from a blood clot, and we all hate Shonda Rhimes for a while because of it.
3. Owen's PTSD (Season 5) It's pretty freaky when Cristina's knight-in-shining-scrubs goes psycho on her in his sleep, nearly strangling her in bed. And all because her ceiling fan reminds him of helicopter blades? We are seriously reconsidering our air circulation methods.
2. Richard's drinking (Season 6) Hospital life seems to bring out the nastiest habits in people, doesn't it? When the stress proves too much, Richard escapes by resorting to a past addiction: alcohol. His life and his career disintegrate in what feels like a slow-motion train wreck.
1. Meredith's surrender (Season 3) After Meredith is knocked off the dock during the ferry disaster, she nearly drowns and the entire Seattle Grace staff struggles to revive her. When she finally recovers, Derek needles her about how it could have happened to such a strong swimmer, and Meredith finally admits that she didn't try very hard to save herself. Ugh — how bleak is that?
10. Cristina's pregnancy (Season 2) All her on-call-room hookups with Burke catch up to Cristina when she realizes she's prego. She doesn't want the baby, and she doesn't want to tell Burke, so she secretly arranges an abortion. Burke finds out anyway when Cristina collapses due to complications with her pregnancy. Not a great start to a relationship.
9. An intern's accident (Season 2) An intern from another hospital falls asleep at the wheel after coming off a marathon shift and crashes into a family of three. A pregnant daughter (one of the family members) dies, and the intern is beset with crushing guilt. Meredith pleads for sympathy from the other interns, saying, "He's one of us." The father of the departed comes to to the intern's room, looking furious, but then cradles the guy's face in a gesture of forgiveness. Powerful stuff.
8. Addison's cheating (Seasons 2 & 3) Not that infidelity is ever cool, but this storyline proves that sometimes both spouses share the blame. It is especially hard to watch Derek kicking a sobbing Addison to the curb in the Season 3 premiere.
7. Thatcher's outburst (Season 3) The relationship between Meredith and her father has never been easy, but it virtually explodes when Thatcher's wife dies and Thatcher blames Meredith before flat-out slapping her. Someone's not getting a Father's Day present!
6. Izzie's realization (Season 5) What starts off as some harmless hallucinations and bizarre ghost sex takes a dramatic turn when Izzie puts two and two together and realizes that she's very ill — as in brain tumor ill. (Denny's not "here for you," Izzie — he's "here for you.")