It could be a dark wizard who has found a way to manipulate Muggle technology for his evil purposes. He could be using it to create chaos in both worlds, which would draw Harry and Fornell together to stop him.
One idea could be that there's a new dark force emerging that is using both magic and Muggle technology in a devious way. Harry, with his magical abilities, and Fornell, with his understanding of Muggle law enforcement, team up. They might start off not trusting each other fully, but as they face various challenges together, they learn to rely on one another's strengths. Fornell could be introduced to the magical world's rules and Harry could learn about Muggle detective methods. They could then use this combined knowledge to track down the source of the new threat.
Lex Luthor from Supergirl's world could be the villain. He could somehow find a way to travel to the wizarding world and team up with some dark wizards. He wants to use magic to enhance his power and take over both worlds. Supergirl and Harry Potter would have to stop his evil plans.
It could be a rogue Death Eater who escaped punishment and has been biding his time. He might have a new, more insidious plan to bring back the dark ways of Voldemort.
There is a possibility that an ancient and powerful dark creature could be the main villain. This creature, long forgotten in the wizarding world, resurfaces and targets Harry's son. It might believe that the boy has some special power or is the key to something it desires. As a result, it lures the son away and hides him in a remote and dangerous place. Harry has to figure out what this creature is and how to defeat it to get his son back.
The Slaughterhouse Nine could be the main villains. Their sadistic and unpredictable nature would pose a huge threat to Harry. Each member has their own unique and terrifying power. Harry would have to rely on his magical knowledge and any allies he can make in Brockton Bay to survive and stop the Nine from causing more chaos in the city.
It could be a descendant of Voldemort. Even though Voldemort was defeated in the original series, his ideas might have been passed down through generations. This new villain could be even more cunning and powerful, and they see Harry Potter, who has been frozen and is now back, as a threat to their plans of total wizarding world domination.
It could be a rogue wizard who was once a student at Hogwarts and has a vendetta against the school. He was expelled for practicing dark magic and now he's back to cause trouble. Maybe he wants to steal some powerful magical artifacts from the school's vaults.
A powerful dementor - like being that has been corrupted by Asgardian dark magic. This entity could be draining the life force of both wizards and Asgardians. It would be up to Thor and Harry Potter to find a way to stop it, as it poses a threat to both of their worlds.
It could be an alternate version of Dumbledore. Maybe in this dimension, he was corrupted by power. He uses his vast knowledge and influence to control the wizarding world for his own ends. He manipulates the students at Hogwarts and uses dark magic in secret while maintaining a public facade of being a great wizard.
It could be Voldemort still. He would be really interested in Mega Man's technology and try to use it for his own evil purposes. Maybe he wants to combine magic and technology to create an unstoppable force.