Let's face it...if there is indeed a Spider-Man 4, it will likely be Tobey Maguire and Sam Raimi's last outing, so let's go all out. After three villains in Spider-Man 3, how do you top it? The Sinister Six. And the way I would do it is this:
There's a "Mystery Man" recruiting low lives and hoods who have been put away by Spidey over the years, thugs that want revenge more than anything, are even wiling to undergo genetic manipulation experiments. This results in the creation of The Scorpion, The Vulture, The Rhino, Electro, and a fifth slot I'll leave open for now.None of these characters need long, elaborate backstories....they don't even really have them in the comics either. They are mostly just thugs with powers. Also along for the ride is Kraven the Hunter, a big name hunter who wants to prove himself by hunting Spider-Man. They are unleashed on Spidey, who after several awesome fight sequences, manages to defeat the Sinister Six ( So named by J Jonah Jameson, who also gives all the members their individual names in the press ) This infuriates the "Mystery Man" who has bankrolled the Sinister Six, and decides to take out Spidey himself. The Mystery Man turns out to be none other than Norman Osborn himself ( how is he back from the dead after being impaled? Hell if I know...he came back after the same thing happened in the comics, so use that explanation, whatever it was ) He was willing to lay low all this time, but since Harry's death ( I haven't read any spoilers for Spider-Man 3, but based on many comments made by James Franco, I'd say it's safe to say Harry bites the big one soon ) Norman is hell bent on revenge. At this point I'd assume that Peter is dating Gwen Stacy ( again, based on Kristen Dunst's comments about not coming back for round 4 ) so The Goblin brings it all back full circle to movie #1, and takes Gwen to the George Washington Bridge this time...and we all know how that turns out.
Peter defeats the Goblin for good this time.
I think this is the only way to top Spider-Man 3. Make it the ultimate Spidey movie, the coda to the whole Raimi Spider Saga. Hell, don't even call it "Spider-Man 4", call it "The Amazing Spider-Man"
There's a "Mystery Man" recruiting low lives and hoods who have been put away by Spidey over the years, thugs that want revenge more than anything, are even wiling to undergo genetic manipulation experiments. This results in the creation of The Scorpion, The Vulture, The Rhino, Electro, and a fifth slot I'll leave open for now.None of these characters need long, elaborate backstories....they don't even really have them in the comics either. They are mostly just thugs with powers. Also along for the ride is Kraven the Hunter, a big name hunter who wants to prove himself by hunting Spider-Man. They are unleashed on Spidey, who after several awesome fight sequences, manages to defeat the Sinister Six ( So named by J Jonah Jameson, who also gives all the members their individual names in the press ) This infuriates the "Mystery Man" who has bankrolled the Sinister Six, and decides to take out Spidey himself. The Mystery Man turns out to be none other than Norman Osborn himself ( how is he back from the dead after being impaled? Hell if I know...he came back after the same thing happened in the comics, so use that explanation, whatever it was ) He was willing to lay low all this time, but since Harry's death ( I haven't read any spoilers for Spider-Man 3, but based on many comments made by James Franco, I'd say it's safe to say Harry bites the big one soon ) Norman is hell bent on revenge. At this point I'd assume that Peter is dating Gwen Stacy ( again, based on Kristen Dunst's comments about not coming back for round 4 ) so The Goblin brings it all back full circle to movie #1, and takes Gwen to the George Washington Bridge this time...and we all know how that turns out.

I think this is the only way to top Spider-Man 3. Make it the ultimate Spidey movie, the coda to the whole Raimi Spider Saga. Hell, don't even call it "Spider-Man 4", call it "The Amazing Spider-Man"