It could be a dark wizard who has somehow learned about the existence of the Mikaelsons and wants to use their power to take over the wizarding world. He might be jealous of their unique abilities and see them as a means to gain ultimate power, so he targets Hope, and Harry has to protect her and stop this dark wizard.
A powerful and corrupt magical being from a long - forgotten realm. This being sees the combined power of Harry and Hope as a threat to his plans of universal domination. He tries to drive a wedge between them by creating misunderstandings and false prophecies, all while secretly plotting to destroy them and take over both the wizarding world and the world of the Mikaelsons.
Maybe a rogue vampire from the Mikaelson's past who has a vendetta against their family. This vampire discovers the connection between Hope and the wizarding world and decides to create chaos in both worlds. He starts attacking Hogwarts students and causing mayhem in the magical world, forcing Harry and Hope to team up against him.
The magic in Harry Potter is more about spells and incantations, while Hope's magic has a more primal and ancestral feel. In a fanfiction, they could complement each other. For example, Harry's Patronus charm could be enhanced by Hope's connection to the spirit world. Or Hope's ability to draw power from the elements could be combined with Harry's knowledge of transfiguration to create new forms of magic.
It could be a power - hungry alien leader who wants to take over Hogwarts and use its magic for their own empire.
A dark wizard from the Harry Potter universe could be the main antagonist. Maybe a follower of Voldemort who escaped the final battle and found his way to Byakko's world. He sees the power of Byakko and wants to use it for his own evil purposes. He could try to enslave Byakko and use its power to take over both the wizarding world and Byakko's realm.
In a 'Harry Potter trained by Goku' fanfiction, the main antagonist could be an evil wizard who has allied himself with dark forces from other dimensions. This wizard could see Harry, with his new skills from Goku's training, as a major threat to his plans of world domination. He might have powers that are a mix of dark magic and some sort of energy manipulation similar to ki. Harry would then have to use his combined magic and Goku - trained skills to take on this powerful and devious enemy.
It could be Voldemort who somehow gets his hands on Oscorp technology and uses it to make his dark magic even more powerful. He would be a formidable foe for both Harry and Peter, as he has his own army of Death Eaters and now enhanced powers. Harry would use his magic and Peter his superpowers to fight against Voldemort's new - found strength.
Most likely, Medusa would be the main antagonist. Her ability to turn people to stone makes her a very dangerous foe for Harry Potter and the other characters in the wizarding world.
In this type of fanfiction, Voldemort could still be the main antagonist. But the way Harry approaches him would be very different. With Riddick's influence, Harry might see Voldemort as just another powerful enemy to be taken down in a more direct, perhaps violent way, rather than through the more magical and somewhat convoluted ways in the original series.
It could be Voldemort and Loki. Voldemort, being the main villain in the Harry Potter series, is power - hungry and wants to rule the wizarding world. Loki, from the God of Thunder universe, is known for his trickery and his own desires for power. They could team up, thinking that they can use each other to achieve their goals. Voldemort could be interested in Loki's ability to deceive and Loki could see the potential in Voldemort's dark magic. They would be a formidable pair against Harry Potter and Thor.
It could be a dark fairy who wants to use the power of both the wizarding world and Pixie Hollow for her own evil purposes. She might try to steal the magic from Hogwarts and the pixie dust from Pixie Hollow to become all - powerful.
The main antagonist could be a dark wizard who has mastered water - based magic and has made a pact with a powerful sea monster. This dark wizard wants to rule both the wizarding world and the underwater world. He sees Harry Potter as a threat to his plans in the wizarding world and Aquaman as a hindrance in the underwater realm.