The answer depends on your relationship to the speaker and the context.
If you want to talk about what you have been doing, then simply say, "I have been xxxxx", or "I was xxxxxx". If you want to just greet someone and not go into details (or if you don't know the person very well), you can reply with something like "Nothing much", "Not a [whole] lot", and proceed with the rest of your conversation.
Sometimes people use "What's up" as a way of asking "What do you need?". For example, if you said to a friend, "Could we talk?", he or she may reply, "Sure, what's up?" meaning: "Yes, what do you need?"