1. When Denny Died
http://negandarylsatisfaction.tumblr.com/post/151195344938/summary-denny-duquette-has-a-crush-on-his
Although Denny was not a main character of the saga and did not appear on many episodes, myself and many other fans fell in love with him. His fast love for Izzy was infectious, and his unexpected death was truly heart breaking. Following his proposal to Izzy, fans thought he would survive his heart failure and marry her. This was the first time fans were crying ugly tears, after he survived his heart transplant and ended up rejecting the organ and passing away.
2. When We Found Out John Doe Was George
https://www.wattpad.com/406100032-multifandom-gif-series-george-o%27malley-8
George O'Malley was the nice one of his bunch, the kind hearted, lovable, Irish boy. Fans were disappointed when they found out he would no longer be a surgical resident at Seattle Grace Hospital, but ultimately found happiness knowing that he was serving his country. But then the tears really started when a man with an unrecognizable face took his fingers and wrote out "007" into Meredith's hands.
3. The Plane Crash
https://www.buzzfeed.com/andyneuenschwander/24-times-greys-anatomy-went-way-too-far
How could this not make it onto the list. It all began with the surgeons boarding a plane to help another hospital with a life-saving surgery of conjoined twins, when all of a sudden the worst thing possible happened. The plane crash resulted in the heart breaking deaths of Mark Sloan and Lexi Grey. Just when we thought we couldn't handle this anymore, Arizona lost her leg and Derek's hand was so badly injured that no one knew if he would be able to operate again.
4. When Arizona Cheated On Callie
https://tenor.com/view/greys-anatomy-callie-arizona-calzona-sad-gif-8484094
The couple that all fans thought could make it through anything, fell apart during an intense rain storm that left the hospital with serious damage. Although we might have thought Arizona and Callie would not make it together after Arizona lost her leg to the plane crash, we were sure that if they could make it through that then they could make it through anything. Ultimately, Arizona ended up cheating with a visiting doctor came to town. After their relationship ended (which eventually started again), fans were very disappointed to see everyone's favorite couple come to an abrupt end.
5. Derek's Death
https://www.pinterest.com/pin/509891989042531856/
Almost all fans thought this day would come; Shonda Rhimes loves to make her fans become extremely attached to characters, and take them away just when we thought they would never leave the show. In Derek's case, I never thought it would take this long for him to be taken off the show since he had survived many traumas. A fan favorite character, left everyone in absolute depression to see Meredith's heart broken into a million pieces after her husband and father of her three children had died. It's a beautiful day to save lives.