I'm sure there plenty of villains to choose from, but I guess most of the most popular ones have been displayed. And some of them are either dead or "retired" now. So Green Goblin, Carnage, Chameleon and Morbius are some of the possible villains for the upcoming game. And while Ock and GG are two of the biggest names, I still think they'll try to set the bar even higher.
So because of that side mission, I was thinking the multiverse could be a part of the game. And Miguel a type of Symbiote Peter/Wraith type of boss.
Anyway, if they want to set up a new Sinister Six, Ock, Green Goblin, Mysterio, Chameleon, Kingpin are some of my choices to make it a little different from the first one. I was a bit disappointed with Mysterio anyway for not being part of the main story.
Last but not least, I would genuinely love Gwen as a playable character. Please, Insomniac.