Formal:
* Que se passe-t-il? (This is the most common and literal translation.)
* Qu'est-ce qui se passe? (This is similar to the above, but emphasizes "what" more.)
* Quel est le problème? (This is more appropriate if you are asking about a specific issue.)
Informal:
* Quoi de neuf? (This means "what's new?" and is a common way to ask "what's happening" in a casual conversation.)
* C'est quoi, ça? (This is used when you're confused or curious about something specific.)
* Qu'est-ce qui se trame? (This is a more playful way to ask "what's happening," and suggests something interesting might be going on.)
Other possibilities:
* Quelle est la situation? (This is used to ask about a general situation.)
* Comment ça se passe? (This means "how is it going?" and can be used to ask about what is happening.)
The best way to choose the right phrase depends on the situation. If you're unsure, it's always safe to use the formal "Que se passe-t-il?"