The Akatsuki could still be the main antagonists. They might see Naruto's new connection to Hades as a threat or a powerful tool they can use. They would try to capture him to either control his powers or eliminate him.
Another possibility is that some of the more traditional shinobi clans in Konoha might see Naruto as a danger because of his relation to Hades. They fear his powers and the unknown elements that come with it. So they could become antagonists, trying to drive him out of the village or keep him from using his powers.
Some of the more malevolent spirits or monsters from the Underworld could also be antagonists. They might resent Percy for being Hades' adopted son and try to undermine him. For example, a powerful undead general who believes he should be the one favored by Hades instead of Percy.
Another option could be some rogue demigods who are jealous of the son of Hades' powers. They might form a group and try to cause trouble for him and Percy Jackson. They could be working with some minor gods who have a grudge against Hades, creating a complex web of enemies.
The village elders could be antagonists. They might see Naruto as a threat due to his devil - like origin and try to eliminate him. They fear that his powers could bring chaos to the village.
It could be Orochimaru. Since Orochimaru is always after powerful ninja and their abilities, if Naruto is now the son of Asuma, he might see Naruto as a new target with unique potential.
Another possible antagonist could be a rogue Titan from the Titan world who somehow makes its way into the Naruto universe. This Titan could be enraged or corrupted and see Naruto as an enemy because of his mixed heritage. It could cause destruction across the ninja world, and Naruto would have to stop it using his ninja skills and Titan powers.
One possible antagonist could be those who oppose the mixing of the Naruto world and the Greek mythology elements. They might see Naruto as an abomination because of his unique heritage as the son of Demeter. Another could be some of the traditional Naruto villains who now see Naruto as an even greater threat due to his newfound powers related to Demeter. For example, Orochimaru might be interested in Naruto's powers for his own evil experiments.
One possible main antagonist could be a rogue ninja who was once an apprentice of Orochimaru and is jealous of Naruto's connection to the Sannin. This ninja might want to steal Naruto's new - found powers related to the Sannin. Another could be a hidden organization that sees Naruto as a threat because of his potential with the Sannin's abilities. They fear he will disrupt their plans for power in the ninja world.
One possible antagonist could be a jealous Roman god who doesn't want Naruto, as the son of Jupiter, to gain too much power. Maybe Pluto, who might see Naruto as a threat to his own domain in the afterlife.
The Akatsuki could still be major antagonists. Their goals of collecting the tailed beasts would put them in direct conflict with Naruto, especially if he has the added power from his relation to Esdeath. They might see him as an even greater threat.
It could be some of the traditionalist ninjas in the Mist Village who oppose Naruto because of his status as the Mizukage's son. They might see him as a threat to their old - fashioned ways.