An ancient evil entity that was once locked away could be awakened by Jesse's wither sickness. This entity doesn't want the sickness to be cured because it plans to use it to spread darkness across the Minecraft world. It starts to manipulate other mobs and characters to stop Jesse's friends from finding a cure.
One plot idea could be that Jesse's friends have to race against time to find a cure. They explore dangerous, uncharted areas filled with hostile mobs in search of a rare ingredient. Another could be Jesse's internal struggle as the wither sickness slowly takes over, and they have to make difficult decisions about whether to isolate themselves to protect others or stay with their friends.
It could be a powerful sorcerer. In the Dark Skies world, a sorcerer with dark magic could oppose Jesse. This sorcerer might be after the same magical artifacts as Jesse or simply wants to rule the Dark Skies with an iron fist.
It could be a new character, like a powerful wizard who has a grudge against Percy for some reason. Maybe Percy accidentally disrupted one of his spells, and the wizard is out to get him, which makes Percy mad.
It could be a lone wolf type of character. This person is a survivor in the same world as Clementine but has gone a bit crazy from all the hardships. They see Clementine as a competitor for resources and decides to shoot her to get rid of the competition.
It might be an accident - causing character. This could be someone who is clumsy or irresponsible. Their actions, even if not intentional, end up causing harm to Judy. For example, they might accidentally start a fire in a place where Judy is, and she gets burned in the process.
It could be Draco Malfoy. In some fanfictions, Draco might be pushed to such an extreme by his family's beliefs that he resorts to physical violence against Hermione. He might punch her out of jealousy or to assert his so - called superiority.
Team Rocket is an obvious choice. They could use some new, devious hypnosis device to control Ash for their own gain, like trying to steal all his Pokémon.
Dr. Eggman could be the antagonist. He's always trying to defeat Sonic, and shooting him could be part of one of his evil plans. Maybe he developed a new weapon specifically designed to take Sonic down.
Another option is a group of anti - magic fanatics. They view Percy's wings as an abomination because they are a result of magic. They hunt Percy down, believing that by getting rid of him and his wings, they are protecting the world from the 'evils' of magic.
It could be an old rival of the Malfoy family. Maybe a wizard whose family was wronged by the Malfoys in the past. This wizard has been biding his time, waiting for the perfect opportunity to strike. Turning Draco into a baby is his way of getting revenge on the family, making them look weak and powerless.