D&D and horror should go together like chocolate and peanut butter. It should. But the two types of game experiences don't usually share the same objectives.
The objective of the D&D style game is to explore and gain treasure. Ruins and abandoned habitations filled with treasure are the default adventure sites. The monsters are incidental. The horror game is about uncovering a mystery that puts the protagonists in contact with the monsters. The cooler and more horrific the monsters, the better. The objective is to survive and resolve the situation (assuming that's possible).
Horror serials reveal the difficulty in rationally explaining why the same set of protagonists keeps running into monsters, and so their structures tend to revolve around two basic forms. The most common approach is to make the group investigative - monster hunters like the agents on The X-Files, or the two guys on Supernatural; relic hunters like Warehouse 13 or Friday the 13th. Some horror serials are locale-based, where the recurring horror situations involve a common nexus, like the house and sanitarium locations of American Horror Story, the village of Sleepy Hollow, or the mansion in Dark Shadows.
My ongoing quest is around reconciling the two game structures - exploration and investigation. My platonic ideal for D&D involves ruins and wealth to recover. I love the D&D sandbox style because the players are placed firmly in charge of planning their excursions. Unfortunately, this mostly precludes the monster-hunter style of campaign, reserving that for games that embrace the 'save the world mentality' like Call of Cthulhu or Trail of Cthulhu. For combining genres, I feel like the ground is firmer by taking a 'relic-hunter' approach, where the players either get a list of potential ruined adventuring sites to target or a list of artifacts to recover. Pursuing their own pecuniary goals is what motivates them to explore and interact with the supernatural world.
Anyway, it seems reasonable that you should be able to build a campaign around a series of ruined locales, each rumored to possess lost wealth, but when investigated, thrusts the players into opposition with eldritch horrors - letting you implement the best of both gaming styles. A bigger challenge for me is whether to place such a game in a historical setting and make it amenable to the traditional 30 x 40 hex map. For myself, one locale where I've done some work is 'Gothic Yorkshire', an interesting area in northern England where there's a density of old ruined abbeys and crumbling castles - it even fits on a standard hex sheet. I'm also perennially drawn to the Mesoamerican ruins of the Yucatan and the world of the Caribbean; sadly, that area is a tad large for a traditional hex crawl, although a 'saltbox' would work just fine.
The LOTFP rules seem to be fairly popular out here in the OSR blogosphere - how are you running your D&D\horror hybrid game? I don't see a lot of discussion around campaign structures so I'm presuming a lot of folks go with the tried and true "plot hook of the week, leads to adventure of the week" style of campaign.