A campaign arc I ran once inadvertently turned into a horror campaign.
The original intent was to have a mini-campaign arc, three or four sessions, to set up a much bigger one. However, it ended up being extended for quite a while, and being the most memorable arc of the whole, 2-year long campaign.
A curse of fecundity had hit a city for an unknown reason, and was slowly seeping outward into the surrounding lands.
It started out as a boon. Seeds would start sprout minutes after they were planted, and plants were producing two, three times as much. Everyone was infected with extra energy, extra life. Animals (and people) had a huge urge to mate, to spread their own seed as well.
Within a week, though, it started to get bad. The bigger plants were so overgrown, they were choking the life out of the smaller ones. Pollen choked the air, so that even people who normally had no trouble were showing Animals (and, again, people) began giving birth months early, leading to stillbirths.
Of course, the fertility and fecundity wasn't limited to crops and animals. Fungus, mold, and bacteria began to multiply and spread like wildfire. Disease was rampant. The choked fields which had once been a sign of great wealth were turned into rotting, fetid sours. People were constantly sick, and doing everything they could to fight off the bacterial blooms growing in their own bodies. Healing magic only seemed to make it worse.
The moment that the players started really getting freaked out was the point when it was so bad that things would start to rot instantly. They would have a combat session, and by the end of the session, the dead were already rotting, mold was growing, and the bodies were bloating up with gas. Fungus and mold began growing up like grass, covering houses, etc.
And then, when they started waking up every morning with mold growing on them...
After the fact, I gave a lot of thought about why this was such a creepy campaign, especially since death was not an uncommon theme for the party. But this was different. The slow, inexorable progression from this wild, fertile "blessing" that was going to spark a new renaissance in a socially decaying city to this soured wasteland was surprisingly jarring. This party dealt with plagues of undeath without batting an eye, but seeing the dead (and eventually even the living) rot and decay before their eyes generated some genuine shudders. And because no one knew how this blessing/curse was being spread, no one wanted to touch anything, to breathe anything in. I'd never seen their characters so skittish before.