I just re-read House of M and realized that if they wanted to break up the marriage, that was a perfect point to do it at. Peter ends the series really shell-shocked after having "lived" through being married to Gwen and having Uncle Ben alive again. I think that would make a growing distance between him and MJ more believable.
Please correct me if I'm wrong but you're talking about the Scarlet Witch "erasing" the marriage, right?
Problem is that they limited it to her erasing just most of the mutants from existence. And both Spidey and MJ are not mutants. So how would you "make it work" in the context of the story. I guess the challenge is how would you do it without changing the whole storyline (that Scarlet Witch changes more than just erasing the mutants but actually changes the whole world's history by erasing certain events including Peter's marriage).
I quite enjoyed reading about Gwen in Spider-Man: Blue