It could be Vlad Masters. Since he's always been interested in Danny's half - ghost state, he might see Sam becoming a half - ghost as an opportunity to gain more power or to use her against Danny. He could try to manipulate her new powers for his own evil plans.
Well, one possible plot could be that Sam gets exposed to some ectoplasmic experiment gone wrong. Maybe she was trying to help Danny with something related to the Ghost Zone and ended up getting infused with ectoplasm. As a half - ghost, she'd have to learn to control her new powers, just like Danny did. She might struggle with the idea of being part - ghost at first, especially if it affects her relationships with her friends and family who might be a bit freaked out.
Vlad could be a great antagonist. He might see the baby versions of Danny and Sam as an opportunity to finally get rid of Danny for good. He could try to use their weakened state to his advantage and steal Danny's powers once and for all.
Well, it could be that there is no traditional antagonist. Sam's betrayal could be the main source of conflict, and she could be seen as the antagonist in Danny's eyes for that time being. But if there has to be another force, it could be the entity that influenced Sam to betray Danny in the first place. For example, a powerful and manipulative ghost that has its own agenda and uses Sam as a pawn.
The Guys in White could be the main antagonists. If Danny becomes evil, they might see this as their chance to finally capture and experiment on him. They would be constantly chasing him, which would make Danny see them as the main obstacle in his new evil plans, and thus they would be the antagonists in the story.
It could be Sam and Tucker. Since Danny has become a villain, his former friends would likely try to stop him. They would be the main antagonists from Danny's point of view now. They would use their knowledge of Danny and their own skills to try and bring him back to the good side.
There could be a rogue ghostly entity that was once a friend or ally of Danny's family. This entity might feel betrayed by Danny's family for some reason and now wants to take revenge on Danny. Since Danny was raised in the Ghost Zone, he is an easy target for this entity. This antagonist could manipulate the other ghosts against Danny and create all sorts of problems for him as he tries to figure out his place in the Ghost Zone and the human world.
Maybe it's a corrupted version of one of Danny's friends. The friend could have been possessed or influenced by some dark power, and then turns against Danny, causing him so much emotional pain that his heart becomes cold.
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 another powerful time - manipulating ghost. This ghost might see Danny as a threat to his own plans of ruling over all time periods. He would try to stop Danny from fully understanding and using his new powers.