Our current (Rolemaster) campaign is set in an East Asian setting, using a mix of Kara-Tur and Bushido maps, and a mix of the Kara-Tur and Freeport timelines. By the time I ran the Freeport adventures the PCs were reasonably high level, so I had to make quite a few changes.
One thing that worked well was inspired by an adventure seed in D20 CoC: there have been a series of murders in Freeport, of increasing frequency, and the location of the murders makes a pattern with the house of the murderer at the centre (although my players never figured out this pattern, or the significance of the frequency - I can't remember now how they found the murderer's house - maybe I stuck it on top of the entrance to the cultists' lair, or maybe the Paladin detected demons).
All that was left of the murder victims was a scalped head - when the PCs eventually found the murderer's house, they were too late to stop the summoning, but found a scene of flayed bodies sitting in a cirlce, with their skins and scalps draped over them like cloaks. A Past Vision spell revealed that the summoner had opened a gate, and the Entity that had come through (T'sen, or Ssendam Lord of the Insane converted into RM stats) had consumed the summoner.
There were various lesser demons to fight, and then a confrontation with T'sen, who had flown out on his Psychic Skiff to observe the lighthouse, waiting for the arrival of the Unspeakable One.
Some other changes made to the basic Freeport scenario included having the island in fact be the body of a dead god (inspired by Requium for a God) who had died fighting T'sen and other voidal entities many thousands of years ago, and who therefore constituted a sort of interface between the material plane and the void (Far Realm). This had been foreshadowed by an earlier meeting with the dead god's mad spirit while the party was on the ethereal plane.
In conversations with the local nature spirits (increasingly driven insane), the PCs learned that the dead god's eyes had opened, with Octobats and other strange beasts coming through. This was foreshadowed with strange catches in fishermen's nets, and climaxed with a fight with a Kraken Drake (8 tentacles, two heads breathing Nether, which in D&D would probably be negative energy).
Thus was sense of wrongness created.
The overall climax I ran a little differently from Freeport - I dropped the McGuffin, and had the PCs disrupt the crystal directly. At the moment of climax, the stars aligned strangely above the lighthouse, and an evil meteor descended from the heavens. Strange beings (the Smoke Generals, lifted from the Druid limited series of comics by Warren Ellis in the mid-90s) wearing the same robes as the monks of the God of Knowledge (an esoteric Buddhis sect, in my version) also arrived on a boat, although the PCs took them for enemies rather than allies and killed them.
Instead of simply telling the players that things felt strange or wrong, I was able to introduce a number of strange effects to reflect the piercing of the barriers between the normal world and the void. Thus, the spell caster with True Sight up (looking for snake men in human form, invisible cultists etc) was able to see through the many layers of the void at once, and use that ability to move through voidal rather than material geometry (basically Dimension Door at will). When the warrior mage was cut, he started bleeding Spiderbats rather than blood. The sea turned to jelly, and the fighters were able to walk on it. The Paladin entered into communion with the Dead God, and was able to persuade him to focus on the Buddha rather than the void, and thus to rise out of the sea to deflect the dark meteor out of the sky to the bottom of the ocean. The location of a dark god at the bottom of the ocean has now become the main campaign focus.
In terms of overall flavour, I would say this scenario was somewhere between Cthulhu and Conan - there were moments of genuine disgust (eg at the flayed murder victims) and a sense of unreality conquering sanity (at the lighthouse climax), but also a lot of dead cultists, demon-slaying and bathing in the ichor of foes (Kraken Drake, T'sen, etc). I think the latter is hard to avoid in D&D-style fantasy.
One other thing I have found works well is drawing direct connections between the voidal beings and the clerical PCs. The latter are Buddhist, and thus believe in overcoming worldly entanglements by achieving enlightenment. It has thus worked quite well to prepare as player handouts a few "mad ravings" written by cultists, which talk about the voidal beings as also having travelled beyond the confines of the mundane, escaping the illusions of the Smoke Generals and realising true emptiness. This generates a sense of disturbance and a hint of corruption around what should be a comforting ideal at the heart of normality, namely, the campaign's mainstream clerical orders.
In core rules D&D, where Buddhist PCs might be few and far between, I think that Boccob, and perhaps Wee Jas, would lend themselves well to this sort of treatment. And clerics of St Cuthbert could be cast as simpletons, whose insistence on common sense blinds them to the deeper truths (of the Far Realm, etc) which can't be denied by those who have experienced them. Like an earlier poster said, to get a CofC feel, its not enough to have bad things - those bad things have to suggest that what we take to be the good things are not really good at all, but are either worthless illusions or already corrupted.
