Maybe the main antagonist is a group of demon hunters. They sense Ciel's transformation into a demon and see it as their duty to eliminate him before he becomes too powerful. They hunt him down relentlessly, making Ciel's life as a new demon very difficult.
It could be another powerful demon who sees the twin brother as a threat. Since he's new to the demon world, this more experienced demon might want to eliminate him.
One possible plot could be that Ciel is forced into a situation where he has to make a deal with a powerful demon. As a result of this deal, he gradually starts to transform into a demon himself. He might struggle with his new demonic powers and the dark desires that come with it.
It could be a rogue AI that wants to use Chell for its own malicious purposes. Maybe it sees Chell as a key to accessing some powerful technology or information.
It could be an ancient and powerful god who has long been plotting against Percy. This god might be jealous of Percy's power and popularity, so he devises a plan to turn Percy into a killer, knowing that it will lead to Percy's downfall and his own rise in power.
Another possibility is that an alien race that Ben has previously encountered and thought was friendly, now turns against him/her because of the change in gender. They might have some strange beliefs or customs that make them view Ben's new form as a threat or an abomination, and thus they become the main antagonists in the fanfic.
It could be a rogue Pokémon trainer who wants to capture Ash - now as Pikachu - for his own collection. This trainer might have a cruel streak and not care about the well - being of Pokémon.
There's a possibility that an evil wizard or scientist who has been studying the Saiyans creates a new form of threat specifically targeting Chichi. This antagonist could be trying to use Chichi's new Saiyan powers for his own evil purposes, like using her to open a portal to a dangerous dimension or to extract the power from her to create a super - weapon.
It could be a power - hungry human who fears Cloud's new Cetra powers. This person might see Cloud as a threat to his own plans of domination and tries to eliminate him before he can fully master his abilities.
It could be Orochimaru. He has always been interested in experimenting with new forms and powers. If Naruto becomes a monster, Orochimaru might see him as a perfect specimen to study or use for his own evil plans.
It could be Team Rocket. Since they always cause trouble for Ash in the original series, in this fanfic, they might see Ash's transformation into a Pokémon as an opportunity to capture him and use him for their evil plans.