The main antagonist could be a powerful ghost who has a vendetta against Danny. Maybe it's a ghost that Danny defeated before, but who has come back stronger and is now seeking revenge. This ghost could hunt Danny down as he runs away, causing all sorts of trouble for him.
Another possibility is that the antagonist could be a group of ghost hunters who don't believe Danny is a good - guy half - ghost. They see him as a threat and are determined to hunt him down as he runs away. They might have some new and dangerous weapons that they use against Danny, and they could be led by someone with a very narrow - minded view of ghosts in general.
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.
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.
A new, powerful ghost that hates the Christmas cheer could be the main antagonist. This ghost could be spreading gloom and trying to cancel Christmas in Amity Park. Danny would have to figure out the ghost's motives and stop it from ruining everyone's Christmas. For example, it might be a ghost who was once a Scrooge - like figure in life and now wants to make others as miserable as he was.
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.
A powerful ghost that has taken over the Circus Gothica and is using it to draw in innocent souls. This ghost might have a vendetta against Danny specifically or just be generally evil and want to spread chaos.
A dark sorcerer from Claw of the Wild who has learned about the Ghost Zone and wants to use its power for his own evil plans. He sees Danny as a threat because Danny has the ability to cross between worlds and might stop him. So, he tries to capture Danny and use his powers to open a portal to the Ghost Zone and unleash all kinds of dark forces.
Perhaps an organization made up of both Pokemon world villains and some of Danny's foes. They could be working together to create a portal that would merge the two worlds in a way that benefits them. They would be the main antagonists as they cause all kinds of chaos, stealing both Pokemon and technology from both worlds to achieve their goals.
It could be a ghost hunter who is specifically targeting Danny because of his new fangs. This hunter might think that Danny's fangs are a sign of him becoming more dangerous and decides to take him down before he causes any real harm.
A powerful ancient ghost could be the main antagonist. This ghost might have been locked away for centuries but has now been released and sees Danny's 'haunted destiny' as a threat to his own plans for the ghost zone. He could try to manipulate Danny's destiny to his advantage.