Most people, when discussing Angels in America, refer to Prior Walter as the play's protagonist. 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 Prophet by the angel makes him sound pretty important, too. Also, in Part Two: Perestroika, Prior gets the big meaningful monologue at the end of the play. Many audience members' hearts probably go out to Prior throughout, as he wrestles with sickness and abandonment.
We should point out, however, that Prior isn't a protagonist in the traditional sense of the word. In Millennium Approaches especially, he doesn't do anything to drive the plot forward. Rather than actively causing things to happen, things happen to him. Louis abandons him as he gets sick, he hallucinates a lot, and he gets dubbed a Prophet by a crazy angel. He doesn't directly cause any of these things to happen. He's just kind of hanging out and lots of terrible and amazing things happen to him.
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, Harper and Joe) and a new one form out of the wreckage (Louis and Joe). Louis and Joe are both protagonists in the sense that they each drive their respective relationships apart – Louis by abandoning his partner with AIDS, Joe by admitting that he's gay, and both by getting together at the end of the play.