One idea could be that the Avengers have to deal with a supernatural force that is causing chaos in the city. Maybe it's a powerful demon that they can't defeat with their usual weapons and tactics. They then seek help from the Supernatural world, like Sam and Dean Winchester, who teach them about exorcisms and using holy water.
Perhaps there's a curse in the Supernatural world that starts affecting the Avengers. For example, they start seeing ghosts of their past enemies. The only way to break the curse is to find a special herb that grows in a hidden realm in the Supernatural universe. So, they embark on a journey with the Supernatural characters, facing various supernatural creatures along the way and learning about the magic and lore of that world.
One idea could be that the Avengers are facing a supernatural threat that they can't understand. So they seek the help of the Winchesters from Supernatural. The Winchesters introduce them to the world of the supernatural, like demons and ghosts. And together they combine their skills, the Avengers' superpowers and the Winchesters' hunting knowledge to defeat the threat.
A really interesting plot could involve the Tesseract from the Avengers. It could be that the Tesseract has some sort of connection to the Darkness in SPN. When the Avengers are trying to protect the Tesseract, they accidentally release some of the Darkness. The Winchesters, with their knowledge of the supernatural, and the Avengers, with their superpowers, must then join forces to contain the Darkness again. The characters could also have some really fun interactions, like Dean being in awe of Iron Man's technology and Steve Rogers being impressed with Sam and Dean's hunting skills.
One idea could be that a powerful cosmic entity forces the Avengers and the Defenders to team up. They have to combine their unique skills, like the Avengers' high - tech gadgets and teamwork, with the Defenders' more street - level and magic - based powers to defeat this entity. For example, Doctor Strange from the Defenders could use his magic to create portals for the Avengers to quickly move around in battle.
One idea could be that a powerful mutant villain emerges who is able to manipulate time. This causes disruptions in both the X - Men and Avengers' universes. The X - Men, with their knowledge of mutants, and the Avengers, with their vast resources and superpowers, have to team up to stop this villain. They start off distrusting each other, especially because the Avengers are sometimes seen as anti - mutant by some in the X - Men world. But as they face challenges together, they learn to work as one.
One idea could be a battle against a common enemy that is too powerful for either the Avengers or the X - Men alone. For example, a powerful alien race that wants to enslave mutants and humans alike. The two groups would have to combine their unique powers and skills to defeat this enemy. Another plot could involve a misunderstanding between the two teams that leads to a brief skirmish before they realize they are on the same side. For instance, the Avengers might mistake the X - Men's actions as a threat to humanity when in fact they are trying to protect a mutant from a rogue government agency.
Another plot could involve the Mass Effect races coming to Earth. The Avengers initially see them as a threat but then realize they are also facing a common enemy, like a powerful alien force that is both a danger to Earth and the Mass Effect galaxy. So they join forces. For example, Garrus could team up with Hawkeye for long - range attacks.
One idea could be that the Avengers are transported to the wizarding world. Iron Man could be fascinated by the magic technology and try to incorporate it into his suit. Another could be that Voldemort somehow gets hold of the Infinity Stones and the Avengers have to team up with Harry Potter and his friends to stop him. Maybe Thor's hammer could be enchanted by a Hogwarts spell to have new powers.
Perhaps there could be a time - travel related plot. A device is accidentally activated in a S.H.I.E.L.D. lab that sends some Agents and Avengers back in time. They end up in a crucial moment in history, like during World War II. There, they meet younger versions of some of the Avengers. They have to work together without changing the timeline too much while also finding a way back to their own time.
One idea could be that the Infinity Stones are scattered across different planets again. The Avengers and the Guardians have to team up to find them before a new villain does. Maybe Thanos has a long - lost relative who is out for revenge and wants to use the Stones' power for destruction.
One idea could be that a powerful cosmic entity threatens both the Avengers' world and the X - Men's. So they have to combine their forces. For example, Iron Man could work with Beast to develop new tech to counter the entity's energy. Another could be a mutant - hating villain who uses some of the Avengers' tech to target mutants, forcing the two groups to team up to stop him.