General greetings and inquiries

How's it going?
(This means "How are you?" not "Where are you going?")
How's everything?

How's life?
 

Asking about present activities
What's up?
 (What are you doing now?)
What's happening?

Asking and telling about recent events
What's new?
 (What interesting has happened since I last saw you?)
Guess what?
(I want to tell you something. Ask me about it.)
(The appropriate response to this is "What?")

A: Guess what?
 B: What?
A: I just got a new job.
B: Congratulations!
 

Bringing up a serious topic
Can I talk to you for a minute?

Do you have a minute?

Got a minute?