A new, original character could be the main antagonist. Maybe a mad scientist who has created a hypnosis - based weapon specifically designed to take down the Powerpuff Girls. This character could be motivated by a desire for power and control over Townsville, seeing the girls as the only obstacle in his way.
Mojo Jojo would be a likely main antagonist. He's always trying to outwit the Powerpuff Girls, and using hypnosis would be just another devious plan in his arsenal.
A powerful music maestro who is jealous of Allegro's natural talent. He wants to steal Allegro's musical essence to make himself the greatest musician in the world and is willing to use any means, including attacking the Powerpuff Girls.
It could be a powerful witch. This witch is jealous of the Powerpuff Girls' beauty and power. So she casts a spell that mutes their beauty, making them look ordinary. This not only affects their appearance but also weakens their powers. The witch wants to take over Townsville while the girls are in this weakened state.
It could be HIM. Since he has always been a major villain in the Powerpuff Girls universe, he might find a new way to turn the girls evil in this fanfiction. Maybe he uses a more insidious form of his magic this time.
Mojo Jojo is a likely villain. He's always trying to outwit the Powerpuff Girls, and hypnosis could be his new devious plan.
One possible plot could be that Mojo Jojo discovers a new form of hypnosis and uses it on the Powerpuff Girls. He manages to make them believe they are his minions at first. But then, Blossom starts to break free from the hypnosis using her intelligence and realizes what is happening. She then tries to free her sisters Bubbles and Buttercup, and they all team up to defeat Mojo Jojo once again.
The plot could be that Mojo Jojo uses a new device to hypnotize the Powerpuff Girls. He makes them do silly things like dance in the middle of the town or speak in a strange language. Then the Professor has to find a way to break the hypnosis.
It could be Mojo Jojo. He's always looking for ways to defeat the Powerpuff Girls, and if he discovers something special about their bellybutton - related powers, he'd surely try to use it against them.
A new superhero from another city could be the main character. He comes to Townsville for some reason, like to learn from the Powerpuff Girls or to help with a particular threat. His unique powers and personality attract the girls, and he becomes the center of their attention in the harem - like situation.
Bubbles is a key character. She has her blonde pigtails and her superpowers. Boomer is also crucial. He has his own set of characteristics that contrast with Bubbles'. In many fanfictions, they are the focus as their relationship is explored, whether it's a friendship that forms unexpectedly or a more complex relationship that develops over time. Other characters from the Powerpuff Girls and Rowdyruff Boys universes may also appear to support or complicate their story, but Bubbles and Boomer are the main attractions.
A young scientist from another town. He could come to Townsville for an experiment or research. His scientific knowledge and curious nature would draw the Powerpuff Girls. Blossom would enjoy discussing theories with him, Bubbles would be charmed by his enthusiasm for discovery, and Buttercup would respect his tenacity in the face of difficulties.