It could be Vlad Masters from Danny Phantom's world. He might follow Danny through the encounter with Gaster and see new opportunities for power in this strange new world. He could team up with some of Gaster's enemies in the new world to cause trouble for Danny and Gaster.
Maybe an experiment gone wrong by Gaster could create a powerful and malevolent being. This being, having no sense of right or wrong, just wants to cause chaos. It could be made up of both the ectoplasm from Danny's world and the strange energy from Gaster's world, making it extremely difficult to defeat. It would target both Danny and Gaster as they are the most likely to stop it.
A powerful ice - demon could be a great antagonist. It could be jealous of Jack Frost's power over winter and Danny's ghost powers, so it tries to take over their powers and rule both their worlds.
One possible plot could be that there is a rift in the multiverse which causes Danny Phantom to cross paths with Gaster. Gaster's knowledge of the multiverse and Danny's ability to traverse different dimensions in his ghost form could be combined. They start to explore the reasons behind this rift and discover that an evil entity is trying to merge different realities for its own malicious purposes. Danny and Gaster then have to use their unique skills to stop this entity and close the rift to restore the balance of their respective universes.
Perhaps a corrupted version of one of their friends or allies. For example, a possessed Tucker or Beast Boy. This would create an interesting dynamic as Danny and Raven would be hesitant to fight their friend at first but would have to find a way to save them from the corruption while also stopping the harm they are causing.
Maybe the main villain is an ancient spirit that was once locked away in a dimension between the two worlds. Danny's accidental crossing of dimensions and Castiel's presence somehow break the seal. This spirit wants to destroy both the world of the living (that Danny protects) and heaven and hell (that Castiel is associated with) in order to create its own chaotic realm.
A group of human hunters who have decided to target Danny's ghost side could be the antagonists. They might be trying to capture Danny and use him for their own experiments. Danny, feeling violated and angry, decides to take revenge by using his ghost powers to outwit them at every turn, and expose their cruel intentions to the people of Amity Park.
Well, it would be the evil Danny Phantom. Consider this: he has gone through some transformation that has made him evil. Now he is using plants in ways that are harmful or against the natural order. Sam, who has a connection to plants and a moral compass, is in direct opposition to him. He creates the conflict in the story by his evil deeds, and Sam has to find a way to overcome his actions, so he is the main antagonist.
It could be a powerful ghost that has somehow made its way into the Young Justice universe. This ghost might be after some powerful artifact that exists in the Young Justice world and Danny and the team have to stop it.
It could be Pitch Black. Since Danny, as Jack Frost, is new to the world of the Guardians, Pitch might see him as an easy target to disrupt the balance. He could try to turn Danny back into his Danny Phantom self or just use his in - between state to cause chaos among the winter spirits and the people of Amity Park.
A new and powerful ghost that Danny has never faced before could be the main antagonist. This ghost could have unique powers that Danny isn't prepared for, and in their first encounter, it manages to defeat and kill Danny. This would set the stage for a story of revenge or trying to bring Danny back.
In the 'danny phantom is a lion fanfiction', the main antagonist could be a group of anti - phantom scientists who capture Danny when he's in lion form. They want to study his unique physiology and use his powers for their own evil experiments. They see him as a threat to their control over the human - ghost interactions and will stop at nothing to keep him locked up and experiment on him.