Maybe in the fanfic, Sasuke has some personality traits that become more difficult for Sakura to handle over time. For example, his brooding nature might start to feel like emotional unavailability rather than just his usual self. This could lead to her regret.
It could be that Sakura realizes in the fanfic that their marriage was more of a childhood crush - based decision on her part. As she grows older, she sees that they have different life goals and values that she didn't fully consider before, and thus regrets the marriage.
In the fanfiction, perhaps Sasuke has a hard time expressing his emotions. Sakura might feel unloved or unappreciated in the marriage. She may have expected more emotional connection and when it doesn't happen, regret sets in.
In the fanfic, it could be that Sasuke doesn't appreciate Sakura enough. She might pour out her love and support for him, but he doesn't return it in the way she hoped. Sakura may have expected a more reciprocal relationship where her feelings are acknowledged and valued. Since that's not the case, she starts to regret her choice of Sasuke.
Often, it starts with Sakura having internal doubts and slowly realizing that things aren't as she hoped in her marriage. For example, she might notice that Sasuke doesn't communicate well with her.
It could be because of a dark power corrupting Sasuke. Maybe an ancient evil force takes over him and makes him see Sakura as an enemy. In some fanfics, this kind of external influence can completely change a character's actions. Also, it might be related to Sasuke's pursuit of power. If he believes Sakura is standing in the way of his ultimate power - seeking goal, he could be driven to kill her.
One possible reason could be Sasuke's focus on his revenge. His thirst for vengeance against Itachi might make him blind to Sakura's feelings and neglect her as he is constantly preoccupied with getting stronger to achieve his goal of revenge.
Maybe to explore different character arcs. The writer might want to see how Sakura would develop as a character if she strayed from her loyalty to Sasuke. It could also be a way to introduce new characters or relationships into the Naruto fanfic world.
Perhaps they leave because they feel restricted in the village. They want to explore the world and grow as ninjas outside the boundaries and rules of the village. They might also want to learn from different ninja cultures and techniques that are not available in their own village.
Sasuke might believe that he's a danger to Sakura. Given his associations with dangerous elements and his own dark powers, he may feel that getting close to Sakura would put her in harm's way. Therefore, he rejects her to protect her. This is a common theme in many fanfics where Sasuke is portrayed as having a strong sense of self - sacrifice when it comes to Sakura.
One reason could be jealousy. If in the fanfic there's another character who Sasuke is close to, Sakura might be rude out of envy. Another reason could be that she feels betrayed by Sasuke in some way, like if he made a decision without considering her feelings. Also, it could be part of her own character development, starting off rude to show her flaws and then changing later.
One possible reason could be that Sakura has finally grown tired of Sasuke's aloof and cold behavior towards her. She might have realized that she has been constantly chasing after him while getting little in return, so she decides to ignore him as a form of self - preservation.