Do it Marvel Adventures (great for all ages!) style.
So, you got the fight against the FF... the Chameleon... The Vulture... the Tinkerer and his minions... Doc Ock... the first game might actually end after the final Doc Ock fight, depending on how many mini-missions they put in between, but I think it would be best if they went on to do the Sandman and then the final few levels/bosses would be the Spider-Man/Dr. Doom issue.
Next game would hit hard and fast with the Lizard, then the return of the Vulture. The Living Brain would be tough to beat, followed with the Human Torch and Electro... The Enforcers and the entire New York mob would be directly followed by a series of fights against a juiced-up Doc Ock.
Third game: Mysterio. For a while you'd have to fight cops cause he frames you... then the Enforcers, the Hulk and the Green Goblin would take a while. Kraven+Chameleon+Central Park>all else. Daredevil and the Circus of Crime would be awesome, and then the return of the Green Goblin w/the Human Torch.
That would be so awesome.