Obviously, Sakura herself is the main character. Naruto could also be in it. Maybe he tries to convince Sakura to stay or he could be the one to help her prepare for her journey. Sasuke might be another character. He could have some influence on Sakura's decision to leave, either by his own actions or just his presence in the village.
Perhaps Sakura leaves the village because she feels out of place. She might have had some falling - out with her friends or just doesn't feel like she belongs there anymore. So, she packs her bags and sets off on a solo adventure to find a place where she can truly be herself.
He could feel a sense of guilt. Sasuke might think that his actions or their relationship issues pushed Naruto to leave. He may then set out to find Naruto, not only to bring him back but also to resolve their long - standing issues. For example, if there were unspoken words or unresolved fights between them, Sasuke would see this as an opportunity to set things right.
Another reaction could be that Sakura tries to follow Sasuke. She believes that she can change his mind or that she can be of help to him. She might leave her own responsibilities behind for a while to chase after him, thinking that their bond is strong enough to overcome whatever is making Sasuke leave.
She may feel angry at first. Sakura is a strong - willed character. She might think that Naruto has made this decision without considering her feelings. In the fanfic, she could go on a rant about how he should have talked to her before making such a big decision.
Well, Naruto could leave the village in a fanfic due to a prophecy. He might believe that leaving is the only way to fulfill a greater destiny that the village can't support. As he leaves, he starts to explore different cultures of the ninja world. He learns about new forms of jutsu and how other villages operate. He could also form a team with outcasts from different villages, and together they strive to change the way the ninja world views things.
Naruto might encounter a group of rogue ninjas. At first, they seem like enemies, but as he gets to know them, he realizes they have their own reasons for being outcasts. They could teach Naruto some unorthodox fighting styles that are not taught in the Leaf Village. Also, there could be a mysterious traveler who has knowledge about Naruto's family that even he doesn't know. This traveler could be the key to unlocking some hidden power within Naruto.
Definitely Naruto and Sasuke. Naruto is the one leaving the village, so he's a central figure. Sasuke, given the 'narusasu' aspect, is bound to play a crucial role too. He could be the one Naruto is leaving behind, or he could be the one who follows Naruto out of the village. There might also be other supporting characters from the Naruto universe like Kakashi or Sakura who could be affected by Naruto's departure.
Perhaps Naruto in the Anbu has a personal mission that goes against the village's orders. For example, he might befriend someone from an enemy village who is actually innocent but is being targeted by Konoha. When the village refuses to listen to his pleas, he decides to leave. He'll use his Anbu abilities to protect his new friend and find a new place where they can both be safe, away from the political drama of the ninja villages.
One possible plot could be that Sasuke leaves Sakura to pursue a solo mission of redemption. He feels that his past actions have left a stain on his honor and he must atone for them alone, believing that being with Sakura would only hold him back from his self - imposed penance.