The Sinister Six would make a great ending, but alas, it cannot happen for these reasons:
Spoiler (Highlight to read):
Doc. Ock is part of the Sinister Six, but he died in Spiderman 2. If they somehow resurect him, he still knows that Peter is Spiderman and would never hurt him.
Then again, they can mess with the comic a bit more and create a completely different Sinister Six. On a side note, anyone else notice how all the villians, so far, of the Spiderman movies have had an inner voice?