Personally, I'd prefer this to last a little beyond just a trilogy, but I would like the first three films to form a lose story arc for Andrew Garfield's Spidey, assuming he stops at three and then we just recast him.
Of that little arc, I feel that Venom would be the best bet as the primary villain. If they go with the spin-off, they can build up to the final film a little more, but the third film needs to be a Venom movie.
I also feel it might be best--no matter how much I don't want this to be the case--to fall onto the Ultimate Universe's Venom. Connect the Venom suit to Oscorp. In fact, connect the Venom suit to the radioactive spider-bite. That way, the Venom story will be the solution to everything. Make it so that Norman Osborn was trying to develop the Venom suit, or that Pete's parents were involved in creating it. Something like that. I'm not the writer, nor have I seen the original film yet, so I can't make any concrete suggestions, just vague ones.
The point is that Marc Webb wants to build up all this intrigue about the "Untold Story." I feel the symbiote should be integral in the whole story, honestly. Then again, that's just what I think. I also think that Norman Osborn should survive until at least the third film to kinda orchestrate the whole story to better hurt Peter, but that's also just me. My second option would be a Sinister Six movie, but I think that, if they continue the film franchise, they could use that down the line.
Also, don't kill all the villains this time...I'd rather them be alive for second appearances and grudge matches down the line.