A group of dark magic - using reindeer could be the main antagonists. Maybe they were banished long ago for misusing their magic, and now they've returned. They target Santa Baby because they know she's important to Santa and the whole Christmas operation. They try to steal her magic to make themselves powerful enough to take over the North Pole.
An ancient snow - spirit turned evil could be the antagonist. This spirit was once a protector of the North Pole but was corrupted by a dark force. It sees Santa Baby as a threat to its new - found evil plans. It tries to stop her and the Guardians from saving Christmas by creating blizzards and other dangerous weather conditions all over the world.
One possible unique plot could be that Santa Baby gets lost in a time - warp and ends up in a different era. The Guardians have to team up to find her and bring her back. Along the way, they discover new magical elements and face off against an ancient evil that was awakened by Santa Baby's time - travel mishap.
It could be a powerful alien warlord who wants to use the dying reader's unique energy for his own evil purposes. Since the reader is in a vulnerable state, this antagonist sees an opportunity to gain power.
Pitch Black would be a likely main antagonist. He could manipulate Jack Frost into turning dark, as he has a history of preying on the insecurities of the Guardians.
Another vampire family that is jealous of the Mikaelson's power and influence. They see the baby as a threat to their future plans. They might try to kidnap the baby and use it as a bargaining chip to gain more power in the vampire world. They would be constantly plotting against the Mikaelsons to get their hands on the baby.
Danzo could be a great antagonist even when Naruto is a baby. He might see Naruto as a threat to his plans for Konoha's future and try to get rid of him secretly while making it look like an accident.
A powerful dark wizard could be the main antagonist. He might be jealous of the dragon rider's powers and the bond with the dragon, and wants to break that bond and steal the rider's powers for himself.
It could be a former ally of the Pokemon Master who has turned evil. Maybe they felt overshadowed by the Pokemon Master and now seek revenge. For example, they might have found a dark artifact that corrupts them and gives them the power to control other trainers' Pokemon.
It could be another dark mage who sees the potential in baby Natsu and wants to use him for evil purposes. This mage might view Zeref as an obstacle in getting to Natsu.
A group of rebels who have different ideas about how to handle the situation of the baby could also be the antagonists. They might think that Effie and Haymitch are too soft or too Capitol - influenced in their parenting of the baby. So they try to take the baby from them to raise it in their own way, believing it will be better for the future of the rebellion and the new society they are trying to build.
It could be Orochimaru. He might see the baby versions of Team 7 as perfect subjects for his experiments. He could try to kidnap them to use their unique chakra or potential for his own dark purposes.