What's up? is a general greeting and is not usually understood as meaning anything.
It used to mean "what's happening" or, when addressed to someone who was upset of crying "what is the matter?".
You'll hear it from time to time, but it is a very common expression. It can be a serious question or the most innocent way of saying hello to someone. For a technical answer, it means "What has developed between the time I haven't talked to you, until now?" I'm exaggerating this answer, it's not this complicated. It just means "What's going on?" If you were asking someone who is working on your car, you'd be asking "How close to finishing my car are you?" or, "Is there something you can't fix?" It's mainly just how are you doing. "What's up with you?" Did I over- answer this?