A confession: this is actually about Revelations only, but had I posted that, it would have spoiled the fact that there are some main-ish character deaths in the game. I figure this is the easiest way around it. If you don't want to know who dies in Revelations, run! Run while you still can!
OK, so there were basically three main character deaths in ACR, and I thought all three were brilliantly done. Here's my ranking of them:
3) Altair -- a brilliant poetic end to the assassin. He's so badass he's prepared to just lock himself in a room, sit down, and die. The transition from him to Ezio was very clever and moving as well.
2) Yusuf Tazim -- they didn't make too much of his death, which just made it even sadder. Possibly the perkiest assassin of all time, my face went like this when I recognised the body --> O_O
1) Subject 16 -- quite apart from the epic music (Scheduled for Deletion), the whole reality collapsing scene was done brilliantly and looked awesome. 16 is still so much of a mystery, but in the end he saved Desmond and died himself, making him an absolute hero. I also loved his closing lines, which I thought were surprisingly poetic for a disembodied madman living inside a computer's guts. I did shed a tear but it evaporated from the sheer awesome.