Well, their friendship could potentially change Sasuke's path. Since Sakura is friends with Itachi, she might be able to communicate better with Sasuke about his brother. For example, she could tell Sasuke about the good side of Itachi that he never knew, which could make Sasuke less vengeful and more focused on rebuilding his clan. This would be a huge shift from the original storyline where Sasuke is mainly driven by revenge against Itachi.
If Itachi and Sakura were childhood friends, it could also impact the Akatsuki. Itachi might have second thoughts about some of the Akatsuki's actions because of his friendship with Sakura, who is a part of the Leaf Village. This could lead to internal conflicts within the Akatsuki, and perhaps some of their plans against the Leaf would be thwarted earlier. Also, Sakura might be targeted by the Akatsuki more because of her connection to Itachi, adding more danger and drama to the overall story.
Their relationship could have a big impact on the medical aspect in the Naruto world. Sakura is a great medical ninja. If she was friends with Itachi from childhood, she might have been inspired to develop new medical techniques to help Itachi with his eye problems or any other ailments he might have had. This could then spread throughout the Leaf Village and improve the overall medical capabilities of the village. And in the grand scheme of things, the Leaf Village being stronger in the medical field could change how battles are fought and how alliances are formed in the Naruto storyline.
Their relationship could have a positive impact on Sasuke. Itachi could use his friendship with Sakura to try and get closer to Sasuke again. Sakura, being Sasuke's teammate, could act as a bridge between the two brothers. She could encourage Sasuke to open up to Itachi, and Itachi could use this opportunity to try and make amends for his past actions. This could lead to a more positive family dynamic for Sasuke.
Their friendship could also lead to a different perspective on the Uchiha clan's situation. Itachi's actions were complex and his friendship with Naruto could have made Naruto more involved in the Uchiha clan's affairs. This might have led to a different solution to the conflict between the Uchiha clan and Konoha, preventing the massacre. In turn, this would have a huge impact on the political situation in the ninja world.
A possible plotline could be that they made a childhood promise to always protect each other's families. When Itachi is faced with the decision to kill his clan, Sakura tries to stop him, not fully understanding the situation at first. This creates a rift between them, but later, as Sakura learns the truth, she tries to help Itachi in her own way, like protecting Sasuke from the shadows as Itachi had asked her to in a moment of desperation.
In many fanfictions, their childhood friendship is the foundation. It makes Hinata understand Naruto on a deeper level. For example, she knows his dreams and his pain from when they were young. This understanding helps her support him better as they grow older and their relationship develops.
Their friendship could change the way Sasuke's character develops. Instead of being so isolated and revenge - focused, with Naruto as a childhood friend, she might be more open to other paths. For example, she could be more willing to stay in the village and help improve it rather than seeking power elsewhere. Naruto, too, would have a different motivation. His drive to bring Sasuke back might be even stronger because of their long - standing friendship, and he would do everything to protect her from the darkness that threatens her.
It might also affect how their friends view their relationship. If Naruto snaps at Sakura in front of others, their friends might try to mediate or take sides. This could further complicate their relationship as they have to deal with not only their own feelings but also the opinions of their friends.
A fan - favorite is 'Shadows and Petals'. This one has a more complex plot. Itachi's past and his role in the ninja world are intertwined with his new - found connection to Sakura. The story is full of action, drama, and of course, the budding relationship between the two.
One possibility for a Naruto and Itachi best friends fanfic could be that Itachi, instead of massacring his clan, finds a way to resolve the conflict with the help of Naruto. Naruto, with his unwavering belief in friendship, could convince the Uchiha clan and the village elders to come to a peaceful agreement. Itachi, seeing Naruto's positive influence, becomes his close friend. They could then train together, with Itachi teaching Naruto some of the more advanced Uchiha jutsu, and Naruto in turn sharing his own unique ninja way with Itachi.
One of the most interesting aspects of Sasuke and Sakura's childhood friendship in fanfiction is how it can be developed in different ways. Some fanfictions might focus on the innocent moments they shared, like when they first met at the ninja academy. For example, they could have bonded over a shared love for a particular jutsu that they saw a teacher perform. This simple connection could then grow over time as they train together and face challenges side by side.
In this scenario, Sakura would be horrified. Her view of Itachi would turn from perhaps a neutral or even positive view (if she had any such view in the fanfiction world) to one of pure hatred. Their relationship would become one of enmity. Itachi using her as a shield would be a huge violation of trust and basic human decency, so she might even try to expose his actions to the other characters, causing a rift in the overall story's character dynamics.