One possible main villain could be Mysterio. He could use his illusions to create chaos in the superhero high school and try to frame Peter Parker for it. Kingpin could also be a good choice. He might see the superhero high school as a threat to his criminal empire and try to take it down. And then there's Electro, who could be causing power outages in the school and endangering everyone.
One plot idea could be Peter Parker trying to balance his normal high school life with the new and crazy superhero high school. Maybe he has a hard time fitting in at first because he's used to being the only 'freak' with powers. Another idea is a big competition between different superhero groups within the school, and Peter has to decide which side to take. And there could also be a plot where a new villain targets the superhero high school, and Peter has to lead the defense.
The Green Goblin could be a great main villain. He might target Peter Parker's daughter to get revenge on Spider - Man. Just like he did with Gwen Stacy in the original story, he could pose a serious threat to her.
It could be Mysterio. He's always been jealous of Peter's connection to Tony. He uses his illusions to mess with Tony's mind and make him forget Peter. Mysterio wants to be the one in the spotlight and sees Peter as an obstacle, so by making Tony forget him, he can get rid of Peter's influence on Iron Man.
The clash of universes. Marvel's Peter Parker in the DC world is a really exciting concept. His different powers and personality compared to DC heroes create a lot of interesting scenarios for the stories.
The Vulture could also be a main villain. He might have a new technology that he believes can only be perfected with the DNA of Peter and Gwen's child. He stalks the family, waiting for the perfect moment to strike and snatch the child away for his evil experiments.
Another one is 'Peter Parker and the DC Superhero High Mystery'. In this fanfiction, Peter is drawn into a mystery that involves some of the most powerful DC characters. It's full of action and the way the author weaves the story around Peter's skills as Spider - Man and the DC world's rules is quite engaging.
A new villain created specifically for this fanfiction could be a fashion - obsessed supervillain. This villain has the power to turn people's clothes into constricting traps. They target Paris's fashion district first, which draws Marinette's attention. When Peter comes to Paris to visit Marinette, he gets caught up in the chaos. Together, they have to figure out how to stop this villain before the whole city is turned into a fashion - related nightmare.
Peter could meet his old teachers. They might be proud of how he has turned out or be shocked to learn about his Spider - Man activities. For example, his science teacher could praise him for using his knowledge in real - world situations. Also, Peter might encounter old crushes. There could be an awkward moment when he sees his high school sweetheart and realizes that the feelings are still there, but things are much more complicated now with his superhero responsibilities.
Venom could be a formidable antagonist. He might be attracted to the chaos and different powers at Monster High. He could start infecting some of the students, turning them into his minions. Additionally, a group of anti - monster humans from Peter's world could find out about Monster High and decide to invade it. They see the monsters as a threat and want to 'cleanse' the school, which would put Peter in a difficult position as he has to protect his new friends from his own kind.
It could be a mad scientist who is jealous of Bruce's work with gamma radiation and wants to create a similar but more dangerous form of it. This new radiation form accidentally makes Peter sick when he gets in the way during one of the villain's experiments.