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The literal same issue applies to heroes.

From experience, it's far more likely that hero players (in a FR-style fantasy world) will take the middle of the road, heed your master NPCs' advice and play to the rules of the setting. They may find their own route through your map, but in games with alignments, innocent villagers being murdered by goblins will be the primary wrong-to-be-righted for heroes, while villains may suddenly have urgent business elsewhere. Maybe they have to contact their temple/investors/accomplices that it has begun, maybe they need mercenaries, or maybe they actually will take on the goblins to use the hero-of-the-day-achievement as a bargaining chip later. If hero PCs later find out that the king's men have been abducting goblins for experiments, that may flip the map. But if confronted with the initial scenario, the heroes (and their token non-good team members) would have to produce a good excuse why they don't act against goblins killing innocent villagers.

The villain on the other hand would start with an entirely own motive that may have nothing to do with the scenario at hand. The goblin attacks are merely a nice distraction to set the plan in motion. They will murder the old (master NPC) ranger who's the last to remember the path to the forgotten temple and instead try to befriend the murderous undead creature inside that would have been hostile to heroes for religious reasons. As a DM, you now have to give the monster encounter more detail and personality. That isn't always as easy as just switching the roles of your master NPC advisor, as different factions have different agendas. It also applies to any neutral parties who may suddenly end up being adversaries or allies, or vice versa. Walls become ramps, ramps become ledges, ledges become walls, paths become pitfalls, pitfalls become paths. All of this has to be considered unless you want to end up improvising. Ultimately, the villain PC may even abandon the scenario because they've come up with a better idea and have no in-game reason to stick around, or because they're being persecuted after their plans were found out. As I said, none of this is a problem if you prepare for it. It's not like evil isn't predictable, but it won't stick to a campaign direction. So, if you as a DM don't know what's coming, you'd have to prepare at least twice as many NPCs and probably additional maps because one PC is an aspiring warlord. A murder hobo, cultist or vampire will produce additional work, all of which has to be written out and double-checked if it works and makes sense - and this is only paper & pencil.

I haven't played Mass Effect, but if those Reapers are the meanies, the goblins in our scenario, making peace would only be a variant of a good playthrough. You probably have the same alliances through most of the campaign and then probably only anger one friendly party if you don't follow through with mass murdering Reapers. Somehow abusing the whole Reaper-situation to take charge of a part of the world or allying with the meanies because you hate the others more would be two different evil scenarios that would not work with the same story moulds.

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BG3 really tests you and annoys you into doing evil things,

Glitches and game mechanics running havoc aside, the times where it was really intentional because NPCs are just so annoying or hateable are actually a great strength of BG3. I can totally subscribe to "enough is enough", but even with my probably 'lawful evil' Tav, I had like a ton of these moments where she probably just said, "Okay screw this, then we'll save the +§%&$ tieflings yet again! Now eat your fish heads!" ...and it's not like Githyanki don't enjoy a good carnage. "Oh, those were Harpers? Sorry!"