Originally Posted by
Mister Mets
Three possibilities depending on what direction Sony (or Disney) wants to go in.
The Continuation:
Amazing Spider-Man 3
This would continue Peter Parker's story. It's been a few years since Gwen died. Aunt May's trying to set Peter up with her niece Mary Jane. Flash Thompson is Peter's roommate having served in the military and lost his legs, all while inspired by Spider-Man.
The main villain is the Jackal, a mad scientist obsessed with Gwen Stacy, performing all sorts of weird experiments. He forms a partnership with the Tarantula, a hitman Spidey had previously dispatched with ease, mutating Tarantula to give him new powers.
The Jackal starts infecting New Yorkers who suddenly gain the powers of Spider-Man. Peter has a bit of a conflict when Flash takes charge, and seemingly becomes a better Spider-Man. MJ gives him a pep talk, revealing that she knows that he's Spider-Man and introduces him to a friend of hers on that planeful of people Gwen saved back in ASM2.
The final fight is Spider-Man VS a mutated dying Tarantula.