If someone whom I DON'T know STARTS a conversation with me for the first time and asks "what's up?" then HOW should I answer?
Interpret "what's up?" as an invitation to talk about whatever you want to talk about. It is not a specific question. The only restriction is that it should be personal. You can talk about your health, about your job, about your family, friends, or about whatever is on your mind, like a book you're reading or activities in which you are participating.