Callbacks as properties can't be set to nil, so things like RemoteFunction.OnServerInvoke = function() end will just have to stay to the old value (the unwrapped function will start throwing relevant errors anyways).
But callbacks like RunService:BindToRenderStep() could be and should be disconnected upon sandbox termination.
This would just require a system to track these callbacks, and while tracking "property callbacks" isn't required, it might still be nice to do in order to determine if a script is still "active" in any way (i.e can have a thread spawned / resumed in any way).
Issues with a system like this would be coordinating everything with all the other worker managers.