One possible main antagonist could be a dark wizard or sorcerer who wants to harness the combined powers of Naruto and Artemis for his own evil purposes. He might see Naruto as a key to getting closer to Artemis and stealing her powers. Another could be a rogue ninja from Naruto's world who has turned against him due to jealousy of his new connection to Artemis.
A powerful demon from the underworld could be an antagonist. This demon might be aware of the unique bond between Naruto and Artemis and aims to break it to cause chaos in both their worlds. He could use his minions to try and separate them and then attack them individually. Also, an ancient god who has a grudge against Artemis might target Naruto as a way to get back at her, seeing him as a vulnerable point in her world.
There could be a group of anti - divine beings who oppose the idea of Naruto being related to Artemis. They might see it as an abomination or a threat to their own power structure. They would constantly try to undermine Naruto and Artemis' relationship. They could use various tactics like spreading false rumors, creating obstacles in their paths, and directly attacking them when they have the chance.
It could be a group of rogue ninjas from Naruto's world who have found a way to cross over to Korra's world and cause chaos. They might want to steal the bending abilities for their own evil purposes.
It could be a creature from Renamon's world that is jealous of the bond between Naruto and his brother. This creature might see their connection as a threat to its own power or status in Renamon's world. So it sets out to break their bond and cause chaos between the two worlds.
Maybe there are some dark forces from the land of Gliats that don't want Naruto's brother to have a connection with Konoha. So they send their agents to cause trouble and try to sever the new - found relationship between Naruto and his brother.
The main antagonists could be a group of rogue ninjas who are after the secrets of the Uzumaki clan. Since Naruto is Mito's brother, they might target him to get to those secrets.
It could be a group of rogue ninjas from a rival village. They might see the little brother as a way to get to Naruto or the Hidden Leaf Village. They could try to kidnap him to use as a bargaining chip or to extract information about the village's defenses.
One possible antagonist could be Orochimaru. He is always interested in obtaining powerful individuals or unique abilities. Koneko's potential might draw his attention, and Naruto would have to protect her from him.
One possible main antagonist could be a power - hungry ninja who wants to use Naruto's connection to the Sage of Six Paths for their own evil purposes. They might try to kidnap Naruto to extract the secrets from him.
The Titans could be the main antagonists. Even though they have been defeated before, some of them might have found a way to return or their followers could be causing trouble. They see Artemis as a threat or a target for their revenge against the gods. Another possibility is a new group of powerful monsters that have banded together and are specifically targeting Artemis for her power and influence among the demigods.
The main antagonists could be some of the more traditional and power - hungry gods. For example, Hera might see Percy as a threat to the order she has maintained for so long. She could try to undermine him at every turn, fearing that his new ideas and his relation to Zeus will disrupt her plans. Another antagonist could be Ares, who might be jealous of Percy's potential power and influence over the other gods and demigods.
One common antagonist could be an old enemy of Artemis who doesn't approve of her marrying Percy. This enemy might be a powerful Titan who sees their union as a threat to his plans for revenge against the gods.