You should never just repeat "What's up" back without first answering the question. That is, it's OK to say "Not much, what's up with you?" but not just point black "What's up" in response.
I would also caution against strongly saying that one should "never" fail to answer the question; in the US at least, it's such a common/generic expression that nobody is likely to be offended if you respond with "hey, how's it going?", or "hey, what's up?", or "what's up with you?".
The situation is similar to "howdy", which almost nobody outside the US south realizes is actually a question (short for "how are you doing?"). Sincerely answering "howdy" with e.g. "I'm fine, thanks" is a bit of a shibboleth that southerners can use to identify each other, but failure to do so is not any real faux pas.