It could be a jealous rival. For example, someone who is envious of the growing relationship between Cynthia and May. This person might try to spread false rumors or create misunderstandings to drive them apart.
Another option is a corporate tycoon. If the story is set in a modern - day urban context, a business mogul who has an interest in the area where Cynthia and May are involved (maybe a neighborhood they are trying to save or a project they are working on). The tycoon would use his money and influence to thwart their plans.
Perhaps a powerful wizard or sorcerer who sees the potential in Cynthia and May's combined powers (if they have any in the fanfic) and wants to stop them from achieving something great. The antagonist might use dark magic to oppose them at every turn.
One possible storyline could be that Cynthia and May meet in a magical forest. They start as strangers but soon discover they have a common goal, like saving the forest from a dark force. As they work together, they form a strong friendship.
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 powerful and greedy trainer could be the main antagonist. This trainer wants to capture Servine and Charmeleon not for the love of Pokémon but to sell them for a high price in the black market. He constantly chases them, setting up traps and using other Pokémon to try and weaken them. This creates a lot of tension in the story as Servine and Charmeleon have to constantly be on the run and find ways to outwit the trainer.
Madara Uchiha could be a great antagonist. He could have somehow gained the power to cross into the Bleach universe and is causing trouble there. Yoruichi and Naruto would have to put aside their differences and combine their skills to stop him. Madara's powerful jutsu and his desire for power would make him a formidable foe for the duo.
It could be an evil ninja who has somehow gained access to the technology from Neo's world and wants to use it to take over the Naruto world. He might be able to create clones using digital technology, making him a very difficult enemy to defeat.
It could be another powerful Pokemon trainer who wants to use Ghetsis and N's relationship for their own gain. Maybe they try to manipulate them into fighting each other so they can take over their influence in the Pokemon world.
A new character could be created specifically for this fanfic. A mad scientist who is obsessed with cross - species experiments. He sees Rachnera as a perfect specimen and wants to use her to create an army of hybrid creatures. He would target both Rachnera and Spiderman as they try to stop his evil plans.
It could be a powerful superhero who is determined to stop Boxman and Venomous. Maybe a hero from another dimension who has heard of their evil deeds and comes to put an end to their plans.
It could be Beerus. Since he is a powerful God of Destruction, he would see the union of Frieza and Cell as a threat to the balance of the universe and try to stop them.
Dr. Wily would be a classic choice. He has the intelligence and the motive to brainwash Mega Man. He could use Mega Man's power to take over the world or defeat his other enemies.