The short answer is that both can be correct. I may be able to tell you if one fits better than another if you shared the context of the phrase.

Question 1 - Correct if you are comparing only two things: - What's the difference between - What is the difference between Correct if comparing more than two things: - What are the differences between Question 2 - These two phrases mean almost the same thing. "How are you?" means some combination of "how do you feel emotionally?", "what have you been doing recently?", or it could even just be a casual greeting. "How are you, really?" means that the question asker probably wants to know how you are emotionally and they want you to be honest. It probably means that they want you to open up to them about of your are doing well or badly. Hope this helps!