Prior Walter is labeled protagonist most often whenever people talk about Angels in America. This is probably because he gets the big moment at the end of Part One: Millennium Approaches with the angel crashing through the roof and all. Being dubbed a prophet by the angel makes him sound pretty important as well. Also, in Part Two: Perestroika, Prior gets the climactic moment of wrestling the angel and rejecting her sacred book. He even gets the big meaningful monologue at the tail end of the play. Many audience members' hearts probably go out to Prior, throughout, as he wrestles with sickness and abandonment.
Although the play is really epic in scale and theme, the basic plot is pretty simple. For the Millennium Approaches part, we're basically watching two couples break up (Louis and Prior and Harper and Joe) and a new one form out of the wreckage (Louis and Joe). In Perestroika, Louis and Joe break up and both unsuccessfully try to go back to their old relationships. Both Louis and Joe drive much of the story throughout Perestroika, which makes us think they deserve a nod in this multi-protagonist play.