Whether to ask someone "What's happening to you?" or "What's happening with you?" depends on the context or the specific situation. If the question is to know the reason or cause of a surprising or puzzling visible behavior or overt action of the person being asked, like grimacing in pain or jumping up and down for no apparent reason, then clearly the question to ask is "What's happening to you?" On the other hand, if the question is about an unknown or unsaid cause or stimulus that's making the person being addressed behave unnaturally or erratically or wince or cry in pain, particularly if there's something wrong internally or mentally or psychologically with that person, then the logical question to ask is "What's happening with you?" How to word the question, whether to use "to you" or "with you," depends entirely on the questioner's perception of the situation.
