I second all the reactions to ALICE BY HEART. I saw a Saturday evening performance and it was clear 30 minutes in that everyone just wanted to leave.
This also wasn't a Broadway production, but my all-time favorite audience reaction was to the Public's JOAN OF ARC: INTO THE FIRE. Prior to curtain, everyone in the theater was buzzing because it was David Byrne's follow-up to the fantastic HERE LIES LOVE. It was also days after the confirmation of Jeff Sessions as Attorney General and "Nevertheless, she persisted" was written on the scrim, a timely reference to Mitch McConnell's chastisement of Elizabeth Warren on the floor of the Senate (eye-rolling now, but at the time it was a bold and culturally relevant choice given the subject matter). It felt like the place to be.
I remember that the show opened with a long (15-20 minute?) production number that covered the whole first two-thirds of her life. Jo Lampert as Joan was very energetic and the ensemble was clearly working hard, but the song sounded like a bad first draft and it was impossible to tell what was going on; it was a mess in every sense of the word and it just wouldn't end. At long last the song abruptly ended and the company huddled together at the center of the stage, arms raised in what was supposed to be victory (I believe they had just won a major battle, but it was impossible to tell what the hell had just happened) and… silence. As the company held their poses, nobody in the theater clapped. Not one single person applauded. After a long 3 seconds (the company was still holding), the woman next to us who had a friend in the show stood up and started applauding wildly, calling for an encore. At this, a handful of audience members gave two or three pity claps, but the vast majority of us were still in shock. And it only went downhill there.
I’ve seen a lot of shows that the audience clearly did not care for, but this was maybe the only time I’ve ever experienced a unanimous rejection of what was on stage.