At first I thought Chameleon wouldn't make a good villain for a Spider-Man movie but now with "Spectacular Spider-Man" and where movie 3 left off I could see him working. MJ and Peter could be patching up their relationship, restarting over, and quilting and sowing back the fragments of their lives they wish they could just not remember. I would introduce a new rival for Pete at the Bugle named Mac Gargan. I would have Kraven and The Lizard be the villains in movie 4, but Chameleon would be in the shadows for a Chameleon/Scorpion/Mysterio team-up.
Chameleon I would have working with Quentin Beck as effects artists on Kraven's show (borrowing stuff from the Ultimate wave). Kraven is hailed by the media as a fraud and a wannabe-Crocodile Hunter but he eventually tries to prove people wrong by going after The Lizard. Then, I would go into "Kraven's Last Hunt." I would have Calypso appear but knowing Raimi, he would make Kraven sort of a vengeful sympathetic villain so I would have it where Calypso is accidentally killed by The Lizard. Kraven swears he'll kill The Lizard no matter how long or what it takes; until he finds out The Lizard is actually Dr. Curt Connors. Seeing as how most of the villains are somehow tied with Spidey or another villain I would have Curt be someone Kraven knows or knew priorally. You could have it where Curt before becoming a reknowned researcher/scientist was first a missionary with his wife or knew the Kravenoffs before all these events unfurled. Kraven would then committ suicide seeing as he almost killed a friend and tells him and Spider-Man he's going to go and be with his dead wife's spirit and rest in peace.
But anywho....as I was saying I would have either Chameleon/Scorpion/Mysterio show up in movie 5 or I would have the symbiote finding it's way to Ryker's and bonding/attaching itself to an inmate named Cletus and thus making him become Carnage. Not needing to use Venom (seeing as he was blown to bits in 3) Cletus would be given all the powers of Venom but also would be given the knowledge of Peter Parker/Spider-Man. Spider-Man earlier in the movie would have busted him for attempted murder and the judge sentenced him to confinement in Ryker's for life. Unfortunately, he escapes, runs amok, goes after Spidey and his loved ones, kills Gwen Stacy and her dad, and it becomes the darkest Spider-Man movie yet.