There are certainly many possibilities. I just do hope that we get to see Spider-Man fighting the Sinister Six, at least once.
Though one thing I have thought about is the "Ultimate Six." This is where Spider-Man was forced against his will to be a member of the group.
In my first post outlining how this thing might work, I gave an example of how Spidey could be used as a periphery character. Perhaps only showing up at the climactic moment of the film to takedown (help takedown) the S6 (see above post). If the film is to lead to a Spidey vs. Sinister Six match-up in the follow-up, we wouldn't want the film to water-down the anticipation for it. You could probably do it without him physically appearing on screen. This is a Sinister Six origin after all, a film from the villians perspective, so this is the most exciting part for me.
One of the ways you could explain the Spidey absence is to make the setting more international. Who says this thing has to be NYC-centiric? If they are going after Oscorp, a multinational corporation, you could hit it in other places. Take-out the knees before trying to cut off the head in New York. Ditto for the Kingpin whose crime syndicate expands beyond NYC. The build-up could be to a NYC climax, at which point Spidey
could appear for his one appearance in person..
Maybe the whole thing takes place in NYC, but the missions/goals of the group are much more covert at the beginning. They wouldn't be the show ponies right out of the gate. They would use slight of hand decoys to distract Spider-Man in one part of the city while they do some destruction somewhere else. It would demonstate the depth and scale of their plan as they move Spidey and the authorities around like pawns on a chessboard. We'd only see Spidey on the news or for a brief moment(s) (like on the groups big screen TV
), or in some distant CGI shot(s), etc.
I personally love the idea of Spidey coming to Osborn's aid as he is about to be taken out by the S6. Again, he helps the guy who has ruined his life by taking down guys who were already ruined by Osborn and himself. So Spidey and Norman win again to the S6, and Norman wins again to Peter.
In the follow-up the S6 will attempt to burn Spidey and the city to the ground. Norman, of course, will have used his resourses to lay low for awhile, but Spider-Man will be the guy who has to clean-up the mess.
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