It could be a power - hungry faction leader who sees Four's little sister as a threat to his or her authority. Since Four is already a well - known figure, the sister might inherit some of his influence, and this leader would want to stop her from causing any changes in the established order.
One idea could be that Four's little sister discovers a hidden power within herself that is different from the factions' norms. For example, she might have an ability to sense when people are lying in a world where truth is highly valued in different ways among the factions.
In fanfiction, Eric's little sister could be portrayed in various ways. She might be a rebel against the strict regime that Eric is often associated with in Divergent. Maybe she has a secret Divergent identity and is trying to hide it from her brother, who is a prominent figure in the faction system.
It could be a power - hungry leader from one of the main factions. For example, a strict Erudite leader who sees the little soldier as a threat to their plans of total control over the society through knowledge and technology.
In some fanfictions, she could be a victim of the faction system in a way that Eric doesn't fully understand. This could create a rift between them as she struggles with her own identity and the expectations placed on her because of her brother's position. It could also be a story of her finding her own voice and fighting for what she believes in despite the obstacles.
It could be a jealous rival of Jaden who decides to target his little sister to get back at him. Maybe this rival is tired of always losing to Jaden in duels and thinks that by causing trouble for his sister, he can distract Jaden and finally win.
It could be Malekith. He might see the sister as a way to get to Thor and Loki and gain power over Asgard. Since she's a new and potentially vulnerable target, he could try to use her in his dark schemes.
It could be a rogue ninja from their clan who has a vendetta against the Uchiha family in general. Since Sasuke and Itachi are already well - known, the antagonist might see the little sister as an easier target to get revenge on the Uchiha. He could try to kidnap her or harm her in some way.
It could be a new neighbor who is jealous of the little sister's relationship with her brothers. This neighbor might try to drive a wedge between them by spreading rumors or causing trouble. For instance, they could tell the brothers that the little sister doesn't really care about them and is just using them for her own gain.
A mischievous fairy who lives in their backyard could be an antagonist. She might be jealous of the attention the kids get and start causing trouble for the little sister. Like making her toys disappear or creating illusions to scare her. This would force the little sister to be brave and find ways to outwit the fairy with the help of her brothers (even if they don't initially believe her about the fairy).
It could be a rogue vampire who has a vendetta against the Cullens and sees Bella's little sister as an easy target to get to them.