A group of corrupt politicians within the village itself could be the main antagonists. They might be secretly plotting to undermine Naruto's authority as the 5th Hokage in order to gain more power for themselves. They could be making deals with other villages or ninja groups that are not in the best interest of Konoha, and Naruto has to expose and stop their schemes.
It could be some of the old enemies who were thought to be defeated but managed to come back. For example, Orochimaru's former followers who still hold a grudge against Naruto and Konoha. They might see Naruto's retirement as an opportunity to strike.
Perhaps a secret organization that had been hidden for centuries and didn't want the new order that Konoha represented. They could have dark magic or forbidden jutsu at their disposal and use it to try and stop the First Hokage from achieving his goals. This would force the First Hokage to not only rely on his physical strength and known ninja techniques but also to find ways to counter the unknown and mysterious powers of this secret organization.
It could be some rogue ninjas who were against the peace treaties after the war. They might form a group and try to disrupt the newly - established peace in the ninja world.
Naruto himself could be a likely candidate. Given his strength, leadership skills, and his dream of uniting the ninja world, he would make a great 6th Hokage.
Sasuke could also be a possibility for the 6th Hokage in the fanfic. He has grown stronger over the years and his unique perspective on the ninja world could bring new ideas to the leadership of the Hidden Leaf. He might start off as a controversial choice but prove himself through his actions in protecting the village and making tough decisions.
Perhaps a powerful and corrupt merchant group could be the antagonists. They are secretly trying to take over the village's economy and resources. They use bribes and blackmail to get their way. The Sixth Hokage discovers their plot and has to stop them without causing too much chaos in the village's economic system. They may also have some ninja mercenaries working for them.
Sasuke could also be a main character. Even though he has his own path, his relationship with Naruto is so deep that he would surely be involved in Naruto's life as the Hokage. He might offer his support or advice when Naruto faces difficulties. And Kakashi, as Naruto's former teacher and the previous Hokage, could also be a key figure in the story.
The remnants of an old enemy clan that the Nidaime Hokage had defeated could be antagonists. They might be seeking revenge for their past losses.
One possible main antagonist could be a shinobi from another village who fears Sakura's potential as Hokage. This shinobi might try to undermine her by causing chaos in her village or spreading false rumors about her abilities. Another could be someone within her own village who has a long - standing grudge against her or her family and doesn't want to see her in a position of power.
Under Naruto as the 5th Hokage in fanfiction, the village would experience a cultural shift. Since Naruto values all kinds of people, the village would be more open to different ideas and ways of life. New forms of ninja techniques might be developed as he encourages everyone to explore their potential. Also, the village's defenses would be strengthened not just by physical means but also by the strong bonds between the villagers, which Naruto would foster.