I mentioned earlier in the supernatural/Leverage hack a couple types of dice that allow you to simulate more dangerous monsters in a fair fight, specifically kept dice (which are used in addition to the usual two) and hard dice (which always roll their max value). In comments, I also mentioned Hurt dice, which aren't rolled, but are treated as part of the pool when you calculate damage. Between these dice and a little bit of manipulation of damage thresholds (that is, how quickly things get taken out), you have the basic tools for modeling most monsters and other nasty beasties, particularity because the bulk of them are purely physical threats.
The bulk, but not all. There are weird powers and other craziness to deal with, but rather than reinvent the wheel, I would just drag Smallville into the mix. Smallville has an incredibly robust system for modeling powers that works in terms of how they work in fiction (rather than in physics) and it would take very little reskinning to translate heat vision over into flaming breath.
For supernatural, the real trick is handling the _weaknesses_ of the various supernatural menaces. A lot of the things that show up are simply too dangerous to fight, even unfairly, unless you have some particular trick up your sleeve.
Now, I mentioned knowledge-based weaknesses before, but it bears repeating. When the weakness is to an action (like vampire's vulnerability to decapitation or zombie's to getting shot in the head) then so long as the characters know this, it is assumed that all their actions are in pursuit of this end. As such, there's no real mechanical concern with making "called shots" - you just fight and do what you can.
Other weaknesses, such as to salt or iron, may benefit from a mechanical representation, but that is thankfully very easy.
A mild weakness pretty much guarantees that you will always have an unfair fight. Going after a werewolf might suck, but if you're armed with silver, it levels the playing field. A mild weakness is generally something that the critter is vulnerable to (so it can't heal or ignore) but which is not necessarily much more dangerous to it. If you need to kill something by stabbing it through the heart with a particular weapon, that's a mild weakness, since you have the means to kill them, but you don't make them any less dangerous.
A medium weakness is like a mild weakness, except the substance actively hurts the creature. Any damage you inflict is considered one die step higher.
A serious weakness will drop the creature with a hit of any quality. Don't bother with damage - if you hit, it's done. Now, "done" may have various meanings - it might mean incapacitating (like holy water to demons) or temporarily dispersed (like hitting a ghost with salt) but it usually means something short of destruction. Serious weaknesses are usually very important to keeping hunters alive, but are rarely a long-term solution to whatever problem is on hand. Serious weaknesses may include things like demon traps. One important note: many serious weaknesses are not also mild weaknesses. That is, they don't necessarily make it an unfair fight.
An absolute weakness is like a serious weakness, but it's final. This happens, and the fat lady has sung. Simple as that.
Now, here's an important thing - serious and absolute weaknesses are very common on the show, but very uncommon in RPGs. The idea of being able to kill a big bad in one shot is at odds with our training that such an action needs to be accompanied by an extensive fight scene. Now, I'm not saying there shouldn't be a fight scene - landing that critical blow can be a big deal - but there's not always going to be one. That might be anti-climactic, but consider the earlier post about structure: if the "hard part" of the adventure has been finding out what's going on, or getting your hand on the weakness, it's ok for the final fight to be short. But if you get right to the fight, making it a cakewalk is satisfying for nobody - the only time you're going to want to do that is if the big bad was a fake-out, and you have something else up your sleeve to fill the time.
Anyway, between the simple dice tricks, Smallville powers, and a basic weakness model, you should be all set for ghouls, ghosts and every other bit of nastiness you wan to throw at your players.