Some possible responses for “What’s up?”

Some possible responses for “What’s up?” are:

Hi
Hi, how are you?
Good
Fine
Chillin
Cool
Nothing
Not Much
Nothing much
What’s up?
Nothing new really
Not a whole lot

Some facetious responses are:
The sky
The ceiling
The roof

The answer depends slightly on the situation, the person who asks and the tone. But generally it is not a question that needs an answer. This is just a greeting. Just say “Hi”

But the situation determines the response. For instance if someone comes in crying and you ask "So, what's up with YOU?", then the question clearly is literal.

For a detailed discussion on the issue, read this article.

For a funny set of responses to "How are you?", go here.
But seriously, you can use one of the following.

How are you?

Good. Thanks.

Fine. Thanks.

Good.  And you?

Fine.  And you?

Fine.  Thanks for asking.

I am good.

I am doing fine.  Thank you.  And how are you?

Fine.  And how are you?

I am alright. (slightly negative)

I am alright I guess.