It could be that Ron's own insecurities and pride are personified as an antagonist. His jealousy towards Hermione's achievements and friendships could be like a dark cloud over him. Severus has to save Hermione from this negative side of Ron. So in this case, Ron's inner demons are the antagonists that Severus must combat.
Well, one possibility could be that Ron has been influenced by a dark magic object. This object makes him act out of character and become a threat to Hermione. Severus, having noticed the strange behavior, intervenes. He might use his powerful magic to break the spell on Ron and thus save Hermione from potential harm.
Maybe a new dark wizard or witch emerges. This character is extremely powerful and manipulative. They target Ron and Hermione because they are Harry's closest friends. By turning them against Harry, this antagonist hopes to isolate Harry and make him easier to defeat. The new antagonist could have some unique magical abilities that allow them to control the minds of others or create very convincing false scenarios.
It could be a new character, like a bully at school who doesn't like Ron's new bad boy attitude and constantly tries to pick fights with him.
A group of Death Eater sympathizers within the Ministry could be the main antagonists. They still hold onto the old pure - blood supremacist ideals and see Hermione, a Muggle - born witch, as a threat. So they fabricate evidence against her and send her to Azkaban to send a message to all Muggle - borns that they are not welcome in the new wizarding order they are trying to create.
It could be the society within the wizarding world that frowns upon same - sex relationships. Even though Ron's feelings are unrequited, the general attitude of the wizarding community might put pressure on Harry, and in a way, act as an antagonist. Charlie would then be rescuing Harry from this external pressure as well as Ron's unwanted romance.
A dark wizard from the past whose secrets are being unearthed because of Hermione's exploration of the Chocolate Frog Card could be the main antagonist. Maybe the wizard was banished long ago and doesn't want his secrets revealed. He could start to influence events at Hogwarts through dark magic, trying to stop Hermione from learning more about him. For example, he could possess other students or create dangerous obstacles in Hermione's path.
It could be a rogue wizard who has a grudge against Hogwarts. He might be using dark magic to create disturbing situations for Hermione and Hagrid to deal with. For example, he could be making the magical creatures in Hagrid's care go wild or messing with Hermione's study time by causing strange noises and apparitions in the library.
Perhaps an ancient evil force that has been trapped in the Sorting Hat for centuries and is trying to use Hermione as a means to break free. The force could start influencing Hermione's thoughts and actions in a negative way, and she has to fight against it with the help of her friends and the positive magic of Hogwarts.
It could be Draco Malfoy. Since Harry and Ron are not friends, Draco could take advantage of their weakened state. He might try to turn them against each other even more, perhaps by spreading false information about one to the other. He could also try to isolate Harry from the Gryffindor group since Ron is no longer on his side, making Harry an easier target for his bullying.
Another possibility is a dark wizard or a group of dark wizards who are after some powerful magic that the Lestrange family has, and Hermione gets in their way as she tries to protect the family or uncover the secrets. They would be the main force that Hermione has to face and overcome throughout the fanfiction.