One of the few things I enjoyed about d20 Modern was a campaign setting called Shadow Chasers. It originally debuted in Polyhedron #150 (attached to the back of Dungeon #92) as a complete/semi-complete mini-game. It was an example campaign in the original d20M core book. I'm not sure if it made any other appearances after that.
The basic premise: D&D style monsters exist in the modern world, but they are veiled by something called the Shadow that makes them appear human or just be unnoticed altogether. In addition, the memories of a human who comes into contact with creatures of Shadow fades or distorts until they don't remember what happened or are able to somehow rationalize it. Some humans gain the ability to see through the illusion and/or keep their memories of their contacts. Some of these people become Shadow Chasers. (Roll credits!)
Use Skyscrapers & Sorcery as the chassis once again. PCs are human, though see below for a possible option.
Add these rules:
The Shadow- monsters are either invisible or appear human, and memory of them fades within minutes of an encounter. Monsters who are invisible become visible when they attack or use a magical ability. Humans searching an area can make an action check modified by wisdom to notice the monsters. To keep their memories, humans must roll a saving throw (modified by Wisdom.) After succeeding at 2d6 saving throws, the human becomes Aware.The GM may also surmise that recordings of Shadow creatures quickly corrupt and become unusable. (Though perhaps certain organizations have technology capable of recording the Shadow.)
Awareness- Characters who are Aware can see through the veil sometimes. They gain +1 on action checks to notice hidden Shadow creatures. Aware characters automatically retain memories of encounters with the creatures. Blessed and Occultists are automatically Aware at 1st level. With the GM's permission, a PC of another class may begin the game Aware.
(Optional rule) Shadow-blooded- Some denizens of Shadow are capable of siring offspring with humans. The blood of Shadow doesn't manifest in every generation, and many Shadow-blooded go their entire lives without realizing what they are.
Here are the three that were originally featured in Polyhedron #150. I've stuck to the concept, rather than the mechanics, as most of them don't translate from d20 to White Box-esque games.
-Spells or abilities that detect denizens of Shadow or supernatural creatures will pick up Shadow-blooded characters, but the connection will be noticeably weak.
-Spells that detect or repel Shadow creatures will affect Shadow-blooded, though they receive a saving throw if none is normally allowed and a +2 to the saving throw if one is normally allowed.
-Shadow-blooded are automatically Aware.
-At the GM's option, Shadow-blooded cannot become Blessed.
Fiend- The character has a demon ancestor. Given that powerful denizens of Shadow rarely emerge so blatantly in modern times, the ancestor might be very distant indeed.
-The character gets +2 to all saving throws vs. fire magic
-The character gets +2 to all saving throws vs. being mentally manipulated
-The character takes 2 points of extra damage from weapons made of silver, cold iron, or meteoric iron.
Lycanthrope- Someone in the character's family line was a lycanthrope of some sort (werewolf, weretiger, etc). While the character is not a full-fledged shapeshifter, she carries some of the beast within.
-The character gets +1 on all action checks involving sight, hearing, or smell.
-The character can see in the dark out to 60 feet, though only in black and white.
-The character can alter their shape, gaining claws and a thick hide. The character has +1 AC and can attack with their natural weapons for 1d6+1 damage (modified by strength.) A character can maintain this for a total number of rounds equal to constitution within a 24 hour period.
-The character takes +2 damage from silver weapons and has a skin allergy to silver.
-The character can fly into a feral rage when hurt or angered. (Reduced to 50% hit points) Unless she can make a saving throw modified by wisdom, the character loses control for 1d6 rounds, assuming shifted form and attacking the nearest creature with their claws. They remain berserk for 1d6 rounds, and can exceed their total amount of shifted time. This saving throw has a -2 penalty if made when the full moon is in the sky.
Vampire- Vampires cannot reproduce, but humans who are bitten multiple times and somehow survive often carry a strange curse that they can pass down through generations.
-The character has +1 to action checks involving sight and hearing.
-The character regenerates 1 hit point per hour. They can still be killed normally, however.
-Sunlight fatigues the character. They suffer -1 to attack rolls, saving throws, and action checks while directly exposed to sunlight. Light created by Blessed miracles affects them the same as natural daylight.
-The character takes 2 extra damage from any weapon made entirely of wood
And here are a couple that I've added:
Dragon- Dragons are renowned for their ability to change shapes. This has resulted in some dragon-human pairings. Dragon blood is extremely latent, manifesting perhaps once a century in a given family. This assumes that PCs are descended from "lesser" dragons as described in the Encyclopia Draconis supplement. (In other words, regular dragons from Swords & Wizardry)
-The character has +1 to all action checks involving financial matters or bargaining.
-The character can automatically assess the value of any object or treasure
-The character has +2 to save versus one of the following types of damage, determined at 1st level and unchangeable thereafter: fire, electricity, cold, acid, poison.
-The character is greedy, and must make a saving throw modified by wisdom to avoid being swayed by the promise of monetary/material reward
-The character takes 2 extra points of damage from weapons of meteoric iron
Giant- Legend has it that some giants used magic to assume human form and took human spouses in the distant past. This character is descended from such a bloodline. Despite being human, people with giant's blood are often "big and tall."
-Once per day, the character may raise their strength score to 18 for 1d6 rounds. If the character's strength is already 18, they receive an additional +1 to any attack rolls, damage rolls, or saving throws/action checks modified by or involving strength. After the strength ends, however, the character takes 1d6-2 damage from overexerting their non-giant body.
-The character has -1 on all action checks that involve fine manipulation or delicate tasks.
This route is more fantasy than horror, which. I'm really warming up to.