Oh, I've got a theory (of course) based on what's currently been going on in Joe Kelly's Spider-Man/Deadpool. And if this theory's correct, then it just further illustrates how devious Mephisto really is.
Remember this scene from One Moment In Time?
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We've been looking at this scene all wrong. The key phrase is not Mary Jane's "you'll leave [Peter] alone for the rest of his days." It's Mephisto saying, "As far as I'm concerned, this never happened." And sure enough, not only does Mephisto make it so Peter and MJ were never married, but we see Peter and MJ never encountered Mephisto as seen during the events of One More Day. Because, of course, if there's no marriage, then there's no deal with Mephisto. Which also means if there's no deal with Mephisto,
then Mephisto is free to interfere with Peter's life again. Except now, Peter's alone, with no loving wife to offer comfort and support.
Flash forward to the events of Spider-Man/Deadpool. During Spider-Man/Deadpool #5, where Mephisto taunts Peter about how he's the "architect of his ultimate fall" that he'll "never find true happiness...because [he'll] always be missing something." We the readers know Mephisto's talking about the erasing of Peter's marriage to Mary Jane. Later, in the last page of Spider-Man/Deadpool #14, it's strongly implied that Mephisto may have orchestrated events to lead Spider-Man down the path to try and kill
Itsy-Bitsy. Well, if Spider-Man commits an act of evil, which murder would most definitely qualify, then wouldn't Mephisto have Spider-Man's soul by default? And Mary Jane isn't there for Peter to set him straight.
In short, Mephisto's been after Peter's soul all along. He just had to get the marriage out of the way in order to obtain it.