The majority of stories you can do with a married Peter Parker and Mary Jane can also be done with an unmarried Peter Parker and Mary Jane in a stable relationship. The exception is the stories that explicitly require the two to be married, which are quite rare.
But with a single Spider-Man, writers have access to other material including but by no means limited to…
- the stories you can only do when Peter Parker is in a stable relationship with someone else (e.g. Black Cat, Sabra, Norah Winters, an entirely new character, etc.)
- the stories you can only do when Peter Parker is in a unstable relationship with someone else (e.g. Black Cat, Sabra, Norah Winters, an entirely new character, etc.)
- the stories you can only do when Peter Parker doesn’t have the love of a beautiful, supportive and good woman.
- the stories you can only do when Peter Parker is explicitly single.
- the stories you can only do when Mary Jane is in a stable relationship with someone else.
- the stories you can only do when Mary Jane is in an unstable relationship with someone else.
- the stories you can only do when Peter Parker is planning to propose to a girl (be it Mary Jane or someone else.)
- the stories you can only do when Peter Parker is engaged to a girl.
and of course,
- Peter Parker tries to get laid (and these will vary depending on the girl.)
Oh and lest I forget,
- Mary Jane tries to get laid (and these will vary depending on the guy.)
There are specific stories you can feature with a Spider Man that you can’t (or definitely shouldn’t) tell with a married Peter Parker. A friend of Aunt May’s sets Peter up on a blind date, and it’s a disaster on every level, everything Peter feared his first meeting with Mary Jane would be like. Peter Parker dates a mutant, SHIELD agent or fellow superhero. Peter’s in love with two girls. He’s in love with a girl who has a loved one—especially a father, though it could be a sibling or best friend—who really hates him. He’s in love with a girl who has a loved one who may be a supervillain.
Peter’s in love with a girl who is in love with someone else. Peter’s in love with a girl who is torn between him and someone else, and eventually chooses someone else. Peter dumps a girl because her moral standards differ from his—she’s upset when he stops to help a man having a heart attack. Peter’s dates a girl who won’t tell her parents about the relationship. Peter dates a normal girl who may be a little too obsessed with Spider Man, or another superhero, especially the Human Torch.
Peter dates an acquaintance’s ex, which leads to an awkward moment in an elevator with Randy Robertson or Iron Fist. Peter worries if he’ll ever find his soulmate. Peter’s depressed after a bad break up. Peter’s aware that if he can’t fix things with his girlfriend, their relationship is over. Spider Man’s aware that if he can’t beat a supervillain in the next six minutes to get to his girlfriend’s younger sister’s wedding in time, his romantic relationship is probably over. Peter Parker has just met a nice girl, and gone on a few dates with her. He is invited to a family dinner. Her older brother (an intimidating looking guy) reacts strangely to him, and whispers in his ear “I know you’re Spider Man. Stay away from my sister.”
Many of these stories have been told before, although the descriptions are generic enough that it can be depicted differently in the future, especially with new characters. Love triangles are sometimes derided, but it’s an awesome storytelling tool. There’s tremendous variety depending on the execution, which includes some of the finest works in literature, as well as many truly great movies (Casablanca, Gone With the Wind, The Graduate, Singing in the Rain, Sunset Boulevard, Some Like it Hot, All About Eve, and that’s just in the AFI top 25.) I’m sure there will be atrociously written love triangles in the future, but there will also be well-deserved Best Picture winners in which the lead has to choose between two suitors. I loved the hell out of The Lives of Others, which certainly had an interesting love triangle, and didn’t come out too long ago.
Given the thousands of variations of “Spider Man fights a super villain” I’m sure the writers haven’t exhausted more than a fraction of the possibilities of Peter Parker gets rejected by a girl. I suspect Peter and a girlfriend have an amicable break up can be done as differently as the dozen or so stories where Peter and his wife argued about the risks he took as Spider Man. New writers can do different things with these plots than the previous writers, the same way Peter David wrote a different Spider Man VS. Vulture story than JM Dematteis, Roger Stern, Mark Millar or Stan Lee.
More options are available to the writers once they know more about the characters, and have the ability to develop them further and use their backstory. The “friends with benefits” relationship with the Black Cat from Amazing Spider-Man #606-630 was a new dynamic, as was the subsequent romantic triangle with Daredevil. And if she regains her memories of Peter Parker, things could also be different in the future. If she’s come to like Peter Parker as much as she has Spider Man, what complications could their relationship have? If Peter Parker suddenly remembers the world before One More Day, how will Felicia Hardy react to Peter’s memories of a happy marriage to Mary Jane? And those are just the possibilities with the one character.
What Would Spidey Do? 
I love u spider man