I think the perfect way to make Spider-Man 4 stand out amognst the series and really kick fans in the balls and kick ass would, if Mysterio could ever be translated onto the big screen, is to have Mysterio in one scene, albiet a nice long action packed scene, to make Spider-Man envision his former enemies gang up on him.
Imagine Doc Ock, Sandman, Venom, and Green Goblin in one scene fighting Spider-Man. It would be something in his mind, almost like a nightmare, but played out on screen.
To put the icing on the cake, and somewhat make amends, Green Goblin could be more menacing and redesigned with a prostestic scary mask and Venom could be bigger. They are nightmarish visions Peter has of Venom and Green Goblin, although for the fans, more along the lines of what the fans were expecting.
This would make for one bad ass scene, incorporate all these villains, and truley kick some ass.