1. Your question should be "What's the difference between these questions?".
"What's your trouble?" doesn't really make much sense... however, "What's troubling you?" would be a lot more natural. It implies that the person the question is directed towards is looking worried, perhaps sick or stressed.
"What's the matter with you?" can mean a lot of different things, depending on the tone in which it's spoken, but usually would give off the feeling that there is something physically wrong with "you", or that they'd done something stupid or annoying. It's pretty much the same as "What is wrong with you?".
"What happened to you?" would imply that "you" is dirty, very sick, or injured looking, and the speaker is either surprised about the appearance of "you", and is concerned about the health of "you", or have a hint of sarcasm.