We Have. A Code. Black.
In Season 2, Meredith held a live bazooka shell in her hands - and inside a patient - and as a result, held the lives of everyone in the hospital in the balance. Just when it appeared all would end well after the bombshell episode - pun intended - Kyle Chandler's bomb squad character was turned into pink mist.
Denny Duquette Dies
The Season 2 finale saw the demise of Denny Duquette (who later returned as a ghost who enjoyed sexual relations with Izzie, which we would prefer not to get into), with far-reaching implications. The charming and tragic patient who won hearts all over the hospital, yet could not keep one beating inside of him, succumbed despite Izzie's best efforts to beat the system and secure a transplant.
George O'Malley Dies
The Samaritan that jumped in front of a bus to save a life at the end of Season 5 and paid for it with his own was not just a random person. John Doe was one of the doctors' own, George O'Malley, who had just joined the army, and even more tragically, the doctors only realized who he was hours later, and could do nothing to save him.
Gary Clark, who lost his wife after Derek failed to save her in surgery, decided he needed payback after she was taken off life support ... so he decided to take the doctors' lives, one by one. He brought a gun inside and started shooting anyone and everyone he sees. Reed and Charles die, Alex and Derek are injured Meredith has miscarriage due to the stress. The Season 6 finale was easily one of the most traumatizing episodes of any show ever.
The Plane Crash
If there's one thing that could top surviving a madman's shooting rampage, it's surviving an actual plane crash, which went down at the end of Season 8. Not that everyone did survive it. Meredith, Derek, Cristina, Arizona, Mark and Lexie all survived, initially, in the woods. Lexie and Mark eventually passed away as a result of their injuries, while Arizona's leg was amputated, Derek's hand was crushed, and everyone was likely scarred for life.
Down Goes Derek
They what???? They killed off Derek via an 18-wheeler crashing into him???? Darn you, Shonda.