I gave this some thought earlier while listening to a podcast and for me I'd say it's almost certainly Avengers: Disassembled - Siege. I loved the Bendis era of Avengers (especially New Avengers), House of M, Civil War and Secret Invasion were huge successes and more importantly fun events that had serious, lasting impacts, Bendis and Brubaker were in the midst of legendary runs on Daredevil and Cap respectively, Ellis delivered Extremis and we also got Invincible Iron Man from Fraction, Messiah Complex and Second Coming (my personal favorite event of all-time) JMS was killing it on Thor and doing great work on Spidey (except for that one thing) such as Back in Black, and Dark Reign was an awesome shift to the status quo.
Tbh, now that I've written it out, I really don't think there's even a close second in contention. Weigh in, folks.