It should be noted that "What's up" in American English doesn't have the same meaning as in British English.
In Brish English, it usually means "What's wrong" or "What's the matter" ("你怎么啦?"). In American English, however, it can just mean "What's new", "What's happening", or "How are you"("最近怎么样?"), as Taryn explained. There may not be anything wrong when it's used in American English.