A powerful alien race could also serve as the antagonist. They might see the combined power of Tony and Hulk as a threat to their plans of conquering Earth. So they try to separate them and take them out one by one. This would force Tony and Hulk to work together even more closely to defeat this common enemy.
Kingpin could be a great antagonist. He already has a history with Daredevil and his criminal empire could pose a threat to both She - Hulk and Daredevil. He might try to use his influence to turn the public against She - Hulk and create chaos in the city.
The main antagonist might be a being from another dimension who is able to manipulate both magic and the Hulk's gamma - irradiated energy. This being wants to use the chaos caused by the meeting of Harry and the Hulk to open a portal to let in more of his kind to take over all the universes. He sets traps for Harry and the Hulk and constantly tries to keep them from working together to stop him.
The Kingpin could be a great antagonist. He's always been a thorn in Spider - Man's side, and his criminal empire and resources would pose a major threat to both Spider - Man and She - Hulk. He could hire super - powered mercenaries to fight them.
The Abomination could be a great main antagonist. He already has a history with the Hulk and his hatred for Hulk could extend to She - Hulk as well. He could be trying to create a new gamma - based weapon to finally defeat the Hulks once and for all.
Lex Luthor would be a great antagonist. He could play on the differences between Batman and Superman, trying to turn them against each other while he pursues his own evil plans. Maybe he creates a situation where it seems like Superman is a threat to Gotham, causing Batman to be on high alert.
Kingpin would be a great antagonist. He already has a history with Daredevil and his criminal empire could easily draw in Spiderman as well. He could use his wealth and influence to create all sorts of problems for the two heroes, like funding new super - villains or using his political connections to turn the public against them.
Another option could be a student from a different magic school who is jealous of Mash's popularity and unique abilities. This student could use dark magic to try and bring Mash down.
Ra's al Ghul could be a great antagonist. His long - standing vendetta against Batman and his vast resources would pose a significant threat. He could also target Black Canary to get to Batman, seeing her as a new and unexpected variable in Batman's world.
The Green Goblin could be a great main antagonist. He is a classic Spiderman villain, and his chaotic nature would clash well with the combined forces of Spiderman and Red She - Hulk. His glider and pumpkin bombs could pose a serious threat to the city and force our heroes to work together in new and interesting ways.
There could be a new, powerful alien being as the main villain. This alien might have the ability to influence Hulk's mind and make him knot Tony. The alien's goal could be to weaken the Avengers by taking out Tony, who is a key strategist and tech - support for the team. The fanfiction could then follow the Avengers as they try to figure out how to defeat this alien and free Tony from the knot.