"What's up?" an informal slang greeting; it's a way of asking "What's going on in your life?" or "What's happening?"

"How are you?" is more personal enquiring about your health and other things in your life compared to "What's happening?"

what's up man is very popular here among friends and people of the same age group. I think it is close to saying E ai cara, beleza? or E ai cara, tudo em cima?