The choice between Orpheus and the Emperor.

If you choose Orpheus then the Emperor leaves abruptly, leading to an ending where someone had to transform into an illithid in order to defeat the Netherbrain. If you choose the Emperor then Lae'zel would loose her chance to free her people and, in her own words, be chased by Vlaakith's people for possibly the rest of her life. It's just a terrible circumstance for at least one character.

I strongly feel that there should've been a persuasion check with the Emperor when choosing to side with Orpheus. The Emperor just up and left pretty abruptly to surrender to the Netherbrain and barely gave you any explanation for choosing to do that. The worst part is that the game didn't even give the player any dialogue choices to persuade them to reconsider which in a game like Baldur's Gate 3, a game that is mostly about dialogue choices, is honestly baffling. When you side with the Emperor, Lae'zel objects but you still get a chance to convince her with a speech check, Voss as well can be persuaded but when it comes to the Emperor you're literally given no chance to do so which is extremely frustrating.

The most prominent reason why I think we should've had an option to stop the Emperor from leaving was that it could've result in an ideal ending for everybody. We could free Orpheus (obviously) and fulfill Lae'zel's goal of freeing her people from Vlaakith, having the Emperor would mean that nobody would need to be turned into a mindflayer in order to defeat the Netherbrain and the Emperor would achieve his goal of being free.

I've had discussions where people would say that there's no chance for an alliance between Orpheus and the Emperor because Orpheus would kill the Emperor at the first chance he got but Orpheus seemed like the kind of person to put the greater good above his personal vendetta and it is to his benefit that the Emperor survives since, once again, we needed an illithid to defeat the Netherbrain which the Emperor is.

Some dialogue ideas I had when trying to convince the Emperor would be something like a "you've asked me to trust you thus far. Now I'm asking you to trust me" or "You've protected me from the beginning. Let me return the favor. I wouldn't let Orpheus harm you".

All in all, it's not the fact that somebody had to make the sacrifice that frustrates me (though I'm still miffed about that too), it's just the lack of any choice for the player to intervene that frustrates me and I hope Larian can add it in at some point.