This from MTV's Splash Page-
When asked about the return of the villainous Doctor Octopus, "No one’s mentioned it, and I think it’s highly unlikely, seeing as he died,” Molina told MTV News during a press event for his upcoming film 'The Sorcerer’s Apprentice'.
“But at the ‘Spider-Man 2′ premiere in London, I turned around to one of the producers and said, ‘It’s a real shame that I died, because I would’ve loved to do another one of these.’ And he said, ‘Oh, characters don’t die in this universe, they just disappear.’”
Molina also went on to say that in future Spider-Man sequels he would prefer to see them concentrate on just one villain as, having two or three of them sort of dilutes the potency of it.”
Considering that 'Spider-Man 2' is considered by many to be the best of the three films, it doesn't seem all that unlikely that Doc Ock could potentially return...