You can't get much more antagonistic than Iago is towards Othello. At the same time, you could make the argument that Iago is the real protagonist, since his character dominates the play and he is the one with the most soliloquies (which is a pretty clear "main character" signal in most Shakespeare plays). But, Iago doesn't really change at all and, as we know, most protagonists undergo some kind of change over the course of a play.
The roles of protagonist and antagonist are more intimately bound together in Othello than in most of Shakespeare's plays. From the opening lines, Iago describes himself not just as Othello's antagonist, but also as a person who wants to completely destroy Othello's life. Iago stays close to Othello so he can rip apart everything that Othello cares about almost from the inside out. Iago understands Othello so well that at some points it seems like he has become a voice inside Othello's head, constantly tormenting him with new doubts.