If they can bring back Bucky Barnes as a Soviet agent with a cyborg arm, anything is possible.
There are those who still think Marvel made a mistake bringing back Norman Osborn to "wrap up" the Clone Saga. But they're sticking with it.
I've wondered if a Gwen-centric take on Batman's "Under The Hood" would work. Gwen returns, knows Peter is Spider-Man, and is enraged he didn't "man up" and kill Norman Osborn. She becomes determined to show Peter Parker "what great power and great responsibility REALLY mean."