It could be a power - hungry scientist who wants to use April's world for his own experiments. He might see the unique elements of the world as a way to gain ultimate knowledge and control.
A long - lost relative of April's could also be the main antagonist. This relative has a grudge against April's family for some past event. They come back to the world with a plan to take revenge and in the process, they cause chaos and destruction. This antagonist would have a personal connection to April, which would make the conflict more intense and emotional.
Perhaps a group of rebels who oppose the current order in April's world. They believe that April and her allies are the ones causing problems and they try to disrupt the peace. Their motives could be based on a misunderstanding or a different view of how the world should be run.
Madara Uchiha is another obvious candidate. Even though he was defeated in the original story, in a fanfic he could be resurrected with even greater power. His Sharingan abilities and his knowledge of the ninja world's secrets would make him a formidable antagonist for taking over the Naruto world. He could manipulate different clans and villages against each other before making his move to take over.
One idea could be that April discovers a new hidden power within her extraordinary world. Maybe she can communicate with the long - forgotten creatures that live in the deepest parts of the world she inhabits.
Perhaps a group of anti - technology extremists could be the main antagonists in an Ultron fanfic. They see Ultron as the symbol of all that is wrong with technology and are determined to take him down, no matter the cost. They might use their own advanced, but more rudimentary, technology to fight against Ultron. This would create an interesting contrast between Ultron's high - tech abilities and their more basic, yet effective, methods.
Another option could be a corrupted version of Asriel. Maybe Alice's arrival somehow stirs up the darker parts of his past and he becomes a force against her, believing she is a threat to the delicate balance in the Underground.
A powerful vampire could be the main antagonist. Vampires and werewolves are often enemies in such fictional settings. This vampire could be after Akakuro's pack's territory or have a personal vendetta against Akakuro himself.
It could be Orochimaru. He's always been interested in unique powers and abilities. The idea of X - 23's mutant abilities and Naruto's jinchuriki powers would be very appealing to him. He might try to capture them both to use in his experiments to gain ultimate power.
A possible main antagonist could be Eris, the goddess of strife. She might be jealous of Aphrodite's beauty and power and see Percy as a tool to disrupt Aphrodite's plans. Eris could send her minions to create chaos and conflict between Percy and Aphrodite, trying to make them turn against each other.
A new character could be created as the antagonist. For example, an Uchiha who has been corrupted by the power of the Sharingan and wants to use Naruto's special Uchiha - related abilities for his own evil purposes. This character could be jealous of Naruto's unique position within the Uchiha - related story and try to take it from him.
It could be a rogue ninja who has mastered parkour to an extreme level. He uses his skills to steal important ninja artifacts and Naruto has to stop him. This antagonist would be very fast and agile, making it difficult for Naruto to catch him using normal ninja techniques.
Frieza could be a great antagonist. He has a history with Broly and would be interested in Bulma's technology. He might see Broly's new alliance with Bulma as a threat and try to break it up. Frieza could also want to use Bulma to create powerful weapons or devices for his own evil purposes.