Terrible luck aside, It seems to mostly be a question of what a "good ending" means to you personally:
If it means that nobody has to transform into a mind flayer, you either let the emperor do his thing or use Gale-bomb.
If it means that all your companion's resolve their character arcs, Gale-bomb isn't an option because blowing him up is just as much a confirmation of his low self esteem as claiming godhood is. But you can still bite the bullet yourself, or let the emperor or Orpheus do their thing.
If you are looking for the overall morally good path - I don't even know. It again seems to depend on personal priorities.
In the end, at least after your first run, it seems to most often become a calculated game of throwing your least favourite character under the bus - which involves a healthy dose of meta gaming if you want to sacrifice Karlach. (She won't be naturally on your team if you don't like her.)
Thinking about sacrifices, the hardest moment for me was during the run in which Gale tried to convince me that allowing him to explode was the best option right before we started climbing the brain stem. Making the choice in the Astral Prism is unpleasant but it is also a fairly quick pain, by contrast if Gale tries to guilt-trip you into allowing him to sacrifice himself, it is a lengthy conversation (three layers if you don't give in) during which you have to defend your decision to preserve the life of one person while endangering the whole world in the process. I hate this conversation and think it is brilliant because it makes the decision to not make a sacrifice suddenly very hard.
