It could be a powerful warlock who has found a way to manipulate time and space. He wants to stop Paige and Prue from joining forces because he fears their combined power. So he creates various obstacles and illusions to keep them apart.
It could be about Paige finally getting to meet Prue in a magical realm. Maybe Prue's spirit is summoned by the Elders to help Paige with a powerful dark force. They might start off as a bit wary of each other, but then realize they can combine their powers in unique ways to save the day.
In fanfic, when Paige meets Prue, it could be a very emotional encounter. Paige might initially be in awe, as Prue was a powerful witch before her. Prue could be portrayed as a guiding spirit, imparting some of her old wisdom to Paige, helping her better understand the family's magical legacy and how to handle certain challenges.
Maybe a powerful rogue ninja who has discovered a way to steal the powers of divine entities. He sets his sights on Amaterasu and Naruto because he knows that if he can combine their powers, he will be unstoppable. He creates various traps and illusions to separate them and weaken them so that he can carry out his evil plan.
A powerful new pirate group could be the main antagonist. They might be after the same treasure or territory as Luffy and Shanks. They could have some unique and dangerous abilities, like the ability to control sea monsters. Their leader could be a former crewmate of a well - known and feared pirate, who has his own vendetta against both Luffy and Shanks for some past reasons.
There could be an ancient force that is awakened by the meeting of Harry and Hela. This force wants to destroy both of them because their combined powers could potentially stop it from achieving its goal of spreading chaos and destruction throughout all the realms. It would use all kinds of devious means to try and separate them and defeat them one by one.
Maybe a powerful warlord from Negan's world who somehow follows him into Artemis' realm. This warlord, with his own thirst for power and destruction, would oppose both Negan (if he starts to side with Artemis) and Artemis herself, wanting to take over the new world he has found.
It could be another god who is jealous of Zeus' interest in Atreus. Maybe a god who feels that Atreus is an outsider and doesn't belong in their divine affairs.
Another possibility is that Death is being controlled or influenced by a greater cosmic entity. In this case, that entity could be the main antagonist. It uses Death as a tool to test or destroy the Avengers. The Avengers would then have to not only deal with Death but also find a way to face this more powerful and mysterious entity behind Death's actions.
Kingpin could be a great antagonist. He has a long history with Daredevil and his presence in Hell's Kitchen could draw Peter in. His criminal empire and power would pose a significant threat to both heroes.
A powerful Decepticon could be the main antagonist. Maybe a Decepticon named Shockwave who is on a mission to find Bumblebee and extract some important information from him. He sees Dante as an annoying obstacle in his way and tries to eliminate him. Shockwave's advanced weaponry and cold, calculating nature would pose a great threat to Dante and Bumblebee's friendship and their goals.