So you want to run a deep and dark exploration of the nastier side of life, but you don't have fragile and vulnerable protagonists whose stark similarity to your own players, with their visceral weaknesses, can really emphasise the terrible aspects of your frightening monsters. Oh no, you've got blood powered vampires or arcana wielding mages or, worse, a Level 13 Dungeons & Dragons party. Simply jacking up the difficulty is just going to make the whole thing frustrating, so what are you going to do? How can you make such people feel vulnerable to the horrors?
Well, there's a few tricks to it. I'm going to have to assume that you're not running a party of anti-heroes who are likely to cheer the monsters on as they eviscerate humanity. If so, the best you're going to get is to pluck at the player's sympathies and make them feel horrified at their character's own antics by making the NPCs very realistic and sympathetic and then nudging their nasty characters to ditch or kill the very NPCs the players have gotten attached to. Do this well enough, and you might get a Heel Face Turn with the anti-heroes becoming heroic because they don't want people to die.
But that's another article.
So, back to the superheroes. If it's a one-off, you could draw the players into it by creating a cunningly well-crafted story involving the loss of their powers - either through divine curses (dropping the 13th level party back to 1st) or conniving the storyline to ensure they expend too much of whatever powers them (vampires with 3 blood; demons without faith; mages without mana). But this is a rather crude tactic that not every player will appreciate, even for a short time.
If you do plan on doing this, explain it to the player so they know it will be temporary and is a chance to try something different. Also, it's best to severely lower the lethality of such an adventure. They've let you undermine their PCs to try out this special episode. Killing them kinda undermines the trust. Situations should be handled so that they often seem close to death, but barring stupidity, they survive. Don't let the players know you're using kiddy gloves. Let them believe they've survived against the odds. That way they won't be cross at you for killing a character that really should've survived that encounter if they'd been given the goodies they've painstakingly earned.
A less crass alternative, is to include very mortal NPCs who make up for their fragility with a sympathetic nature. This doesn't mean making them goody-two-shoes. This means making them interesting in a way that catches the player's attention. The bitchy cheerleader-type who struggles to keep up on a broken leg and fights with tooth and nail might gain enough respect, even if she was initially unlikeable. Have a think about your players and what would resonate with them and then create NPCs accordingly.
Then threaten the hell out of those NPCs. Be cautious about letting them drop like flies and instead set up the situation so that the PCs always had a chance to save them, but that they may fail. You can, of course, injure and mutilate them as much as you like. The exception to this is if you have a big Set Piece Death, in mind, though keep these rare and only use them if they're incredibly appropriate. In truth, unless there's some supernatural reason why they must die (i.e. they're already dead and are killed again and again because that is what they're fated to do), then you should always allow for the chance the PCs will keep them alive. However small that chance might be.
The enemies should be sparse on the ground to keep the superheroes from getting used to fighting them.
The enemies could be designed to discourage attacks in one of two ways: Resistance or Power.
With Resistant monsters, perhaps they're immune to magic (so spells fizzle on them) with massive regeneration and a lot of hit points. The players strike them a few times, realise they can't kill it with a frontal assault, and look elsewhere for the answer. This can be perfect if you want to force them to discover back history on the monster and learn its bans that might strip away certain abilities. The Forbidden Siren series on Playstation are a good example of a resistant monster. They're at least as strong as you but you can only ever beat them unconscious. They'll always get back up again.
With Powerful monsters, they may not have a lot of hit points but they pack one hell of a punch. Make sure you showcase their raw might by showing the remains of a more powerful party of adventurers spattered across a room (perhaps have a spellbook show they can cast 7th level spells and yet still died). You could even show them in action against property, ramming into the side of a building and destroying it, before ambling away. Or show the creature destroy an over-eager and reasonably strong individual with a single flick of a tentacle. This is quite good if you want a stealth game or one involving a lot of tactics. It's often best not to make the Powerful creatures too perceptive or else the PCs will die unless they happen to be stealth monkeys.
And, of course, remember to use all of the tricks mentioned in my other survival horror articles. They can all help create that sensation of dread no matter what the PCs are capable of doing.
So, I hope you found that useful. If you'd like to read more in the series, you can find them here.