In the US, certain things are ritual greetings that follow a standard script. Deviating from it is considered a bit weird (but it’s also common, and possible to get away with. I deviate from it often).
“How are you?” is not usually intended as a real question. The expected answer is along the lines of “Fine, and you?”
The default answer to “what’s up?” is something like “nothing”, or “Not too much; yourself?”. It’s considered slightly less weird to answer