I had to go with Green Goblin. Only one to complete wreak havoc Peter's life both in and out of costume. In fact, how many of them were also running the Avengers and SHIELD (well, hammer) during Dark Reign? When he made his return from the "dead" in the late 90s, the tagline was something along the lines of "Spider-Man's greatest enemy isn't the Green Goblin, it's Norman Osborn."
Also a big fan of Sandman. Especially liked him when he was playing the hero with Silver Sable and the Wild Pack.