It could be a group of pure - blood supremacists. They might see Hermione's transformation as an abomination and try to 'correct' it or get rid of her. They could spread rumors about her and try to turn the wizarding community against her in her new form.
A jealous student could also be the antagonist. This student might be envious of Hermione's new abilities and popularity among the magical creatures. So, they try to find a way to reverse her transformation or cause trouble for her while she's in her magical creature form.
One idea could be that Hermione turns into a phoenix. She could then use her new form to fly around Hogwarts, exploring places that are usually off - limits. She might also discover she has the power to heal with her tears, like a phoenix does, and help injured students or magical creatures on the school grounds.
One could be the Thestral. Since Hermione is very intelligent and curious, her discovery and study of Thestrals, which are invisible to those who haven't witnessed death, could be an interesting plot. Another could be the Niffler. Hermione might have an adventure trying to keep a Niffler from stealing shiny things in a museum or a wizard's home. And the Phoenix is also a great choice. Hermione could be involved in a story where she helps a Phoenix that is in trouble, perhaps injured or lost, given her kind-hearted nature.
Well, Hermione is known for her determination. In a fanfiction involving magical creatures, this would mean that if she set out to protect a certain creature, like a Phoenix that was in danger, she would not give up easily. She'd fight against any threats, whether it be dark wizards or harsh environmental conditions. Her loyalty also plays a part. If she befriends a magical creature, like a Kneazle, she would be loyal to it and do whatever it takes to keep it safe. Additionally, her inquisitiveness would lead her to constantly seek new knowledge about magical creatures, which could lead to all sorts of adventures and interactions.
It could be a hippogriff. Hippogriffs are very majestic and intelligent magical creatures. In the Harry Potter series, Buckbeak was a hippogriff that Harry had an encounter with. It has the body of a horse and the wings and head of an eagle, which makes it both powerful and graceful.
Another possibility is an ancient evil that has been awakened. This entity might see Hermione as a threat because of her potential power. So it curses her to stop her from growing stronger. In this case, the antagonist would be very powerful and mysterious, and Hermione and her friends would have to do a lot of research and exploration to find a way to defeat it.
A powerful and corrupt Pokemon trainer could be the antagonist. This trainer is jealous of the boy's unique transformation into a Pokemon. He wants to use the boy's powers for his own gain, like winning all the Pokemon battles and championships. So, he hunts the boy down, causing all sorts of trouble for him during his journey as a Pokemon.
Maybe Team Rocket could be the main antagonist. They might see Ash's transformation as an opportunity to finally capture Pikachu. Since Ash is in a more vulnerable state as a girl, they could try to use different tactics to take advantage of the situation.
Perhaps a jealous trainer. This trainer has always been envious of Ash's success and now that Ash is in a vulnerable state as a Zorua, the trainer sees an opportunity to get rid of him for good. The trainer could try to use his own Pokémon to capture Ash or even harm him, making the trainer a formidable antagonist in the story.
The antagonist could be a group of bullies in the story. They pick on Percy because he is now a child and seems weaker. They don't know he is actually Percy with all his heroic qualities. They constantly harass him, steal his things, and try to make his life miserable. This forces Percy and his friends to come up with strategies to deal with these bullies, which could include using Percy's unique skills even in his child form, like his ability to talk to sea creatures to get help when the bullies try to corner them near the water.
Perhaps an evil mage who actually intended for the transformation to go wrong on purpose. They might want to use Sans' new female form to cause chaos in the Underground. They could be trying to manipulate Sans into doing bad things or using her to get to other important characters.