I'm running an Emerald Spire campaign that was supposed to have a significant amount of home-brew elements thrown in. I really liked the town & came up with many quests to help the various friendly NPC's in town. I told the players right at the beginning that I really wanted to play the game that way rather then doing a straight dungeon crawl.
The players decided after the first 2-3 games that they'd rather distract & rob all of the NPC's whenever they need to resupply, rather than doing the side quests I came up with so the friendly NPC's would give them loot & heavily discounted items. (I got to do ONE side quest near the beginning of the campaign and they reacted by tying up the NPC alchemist after the quest was over & stabbing him repeatedly in the kneecap while threatening to kill him)
It's always a consensus among the players that they'd rather do things that way so I never really pushed my home-brew side quests on them. (I'm a fairly new GM, & a bit of a pushover)
But there was one plot line I was really wanting to run. I'd been planning it since they were around level 2. And I told my players at the end of every game for about 4 weeks that I was going to introduce an important NPC, that I would really really like them to not kill. The NPC was supposed to kick off a political subterfuge plot that would have made great use of each of the players class skills & was going to cumulate in the final game session with all of the evil hell-knights being condemned forever to hell & the town being freed from oppression.
Instead, they decided as a group that the gunslinger should be allowed to coup de gras the NPC in the back of the head & continue along with the dungeon level they were on. I spent the rest of the game half paying attention to what they were doing as I tried to think of a way to get the plot back on track. At the end of the game they had gone back to town and distracted the guards by sending them on a wild goose chase. I assumed that they were just going to rob the town again.
The next weeks game started and they decided to kick down the door of the head commanders office while she was doing paperwork & kill her by peppering her with bullets. I was caught completely off guard! I didn't even know until about 5 min before the game started when one of my players told me he'd brought all of his human minis because they were taking the town that game. I'd spent hours drawing intricately detailed maps of all 4 floors of the main citadel and I didn't even get a chance to use them because I had no flippin' idea they were planning to do that! I tried to make it very clear that they weren't supposed to be doing that by asking over & over again "Are you sure you want to do this?!", and having the main NPC they were killing do nothing but beg for her life & drink healing potion after healing potion. But they all agreed that that's what they wanted to do and they wanted to do it like that and right then.
Everyone said they had a good time, but it just felt so unsatisfying to me to just have a pair of gunslingers riddle the npc full of bullets while no one else really got to do anything.