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Unless you're trying to play a wacky game. Then it quickly turns into game of thrones.
Once the party finds that one NPC they care about.
My old pandemic D&D group was the best. They cared about everything. But I remember specifically one time they arrived at a large party. I was describing the scene- large tables set with food, small groups of people mingling, and off in the corner you see a man talking to a woman, her back is against the wall and he's got his arm on the wall so he's kind of trapping her there. She looks uncomfortable.
The players all beelined to those two to rescue the NPC from the guy. Oh, Pretty Paul. They hated him so much. Such a good villain. (Started as a riff on Handsome Jack, and it worked so well. One of the players wrote a song about how much they hated Paul)
My players once used charisma and magic to basically trick/enslave some generic box to participate in everything for THE WHOLE CAMPAIGN. I kept trying to kill him and when that didn’t work I tried to make them feel bad about the situation because he had a family at home that had no idea where he was and when I finally managed to kill him they just brought him back from the dead. He was a level 4 night and they were level 18 when the campaign ended