"How do you do" is extremely formal, most people don't say this anymore. "How are you" is good. It's not extremely formal, but it's also not too informal. "How's it going" is slightly less formal than "how are you," but otherwise it's similar. "What's up" is very informal, and you wouldn't say it to someone older than you, or to a "higher-up" like a professor, your boss, etc. However, if the person you're talking to is a friend around your age, "What's up?" is probably the most commonly used greeting by (young American) English speakers. The most common answer to "What's up?" is "Nothing." Common Scenarios: You talking with your boss: "Hi (boss's name), how are you?" "Good, you?" "Good, thanks." You talking to someone you don't know very well: "Hi, how are you?" (Or, "Hi, how's it going?") "Pretty good, you?" "Good, thanks." You talking to your close friend: "Hey, what's up?" "Nothing" (Or, "Nothing, just going online" or "Nothing, just going to lunch" or "Nothing, just screwing around") "Cool, later." "Later."

if you have new friend, better you use " how are you " or " how do you do ".