It could be Bellatrix Lestrange. Since she is a Death Eater and has a personal vendetta against Sirius, she would be a great antagonist. She might try to kill Sirius again and also target Harry to please Voldemort.
The main antagonist could also be a new dark wizard or witch who has a connection to Sirius's past. Maybe someone from his family who was always jealous of his powers and now wants to use Harry to get to Sirius. This new character could have a hidden agenda that involves taking over the wizarding world and sees Sirius and Harry as the biggest threats to their plans.
Maybe it's a group of dark wizards who believe in a more extreme form of pure - blood ideology. They see Arcturus Black as a traitor for teaming up with Harry Potter, who is a half - blood. They plot to take over the wizarding world and eliminate anyone who doesn't fit their idea of a pure - blood wizard.
It could still be Voldemort. Even though the focus is on Harry and Nagini, Voldemort is Nagini's master and the main source of evil in the Harry Potter world. He would likely try to stop Harry from getting too close to Nagini or from finding out any secrets Nagini might hold.
It could be a dark wizard who is jealous of the bond between Harry and Lily. This wizard might try to break their connection and use Lily's power for his own evil purposes. Maybe he wants to control Lily's magic, which is known to be strong, to achieve domination over the wizarding world.
It could be Voldemort who somehow follows Harry into the realm of the Morrigan. His dark magic could disrupt the balance there and make him a common enemy for both Harry and the Morrigan.
There could be a group of anti - magic fanatics in the fanfiction. They see Byako as an abomination because of his strange powers that don't conform to the normal rules of wizarding magic. They also view the Hogwarts students' acceptance of Byako as a sign of the corruption of magic. So they set out to eliminate Byako and anyone who stands in their way.
It could be a dark fairy who wants to use the power of both the wizarding world and Pixie Hollow for her own evil purposes. She might try to steal the magic from Hogwarts and the pixie dust from Pixie Hollow to become all - powerful.
Maybe the main antagonist could be Ra's al Ghul. He's always interested in power, and if he got his hands on some magic from the Harry Potter universe, he could become an even greater threat. He could try to use the magic to bring about his vision of a 'perfect' world, which would be at odds with both Harry's and Nightwing's ideas of justice. So they'd have to join forces to stop him from achieving his goals.
A dark wizard from the Harry Potter universe could be the main antagonist. Maybe a follower of Voldemort who escaped the final battle and found his way to Byakko's world. He sees the power of Byakko and wants to use it for his own evil purposes. He could try to enslave Byakko and use its power to take over both the wizarding world and Byakko's realm.
Most likely, Medusa would be the main antagonist. Her ability to turn people to stone makes her a very dangerous foe for Harry Potter and the other characters in the wizarding world.
It could be a power - hungry alien leader who wants to take over Hogwarts and use its magic for their own empire.