I recently read an excellent review of the game Crypts & Things Remastered - I'll link to it when I can find the review again.
One element of the rules the review discussed is that, essentially, only heroes get to make saving rolls. The gap between heroic protagonists and everyone else is they get a chance to shrug off spells, resist poison, survive that fatal disease.
I think this is a neat idea easily portable to any game that features heroic protagonists, nameless NPCs meant to be cannon fodder, and terrifying foes meant to be dealt with only by heroes. Any game system, too. AD&D? Same as Crypts & Things. Call of Cthulhu? Only investigators get a chance to avoid SAN loss. And so on.
For GURPS, this fits into a heroic adventuring game quite nicely as a genre switch, much like rules for fodder. You can simply add this:
Only Heroes Resist! - Nameless foes and minor NPCs never succeed in rolls to resist supernatural powers, social skill rolls, poison, disease, and so on. They may appear to try to resist, but they always fail. As long as the roll for the skill, spell, etc. succeeds and there is a chance they could fail, they do. They can freely deploy such powers against each other will the same effect, but if they target PCs and important NPCs, those subjects get to resist normally!
For DF, expand that by saying that Fodder monsters never succeed in resistance rolls; Worthy may (the GM should decide how strongly to implement these rules), and Boss monsters always get to roll.
This actually would have the effect of driving up the effective power level of PCs without increasing their points. A low skill such as Intimidation-12 or Sleep-14 would be plenty - it's always going to work on the weaker foes. Truly worthy opponents and actually scary monsters will provide a challenge.
Of course, this won't necessarily stop players from thinking, "I need Sleep-30 so I can use it on boss monsters!" but it does mean they're wasting points and effort.
It also means you don't need to scale up challenges - you can effectively play at lower points. If having, say, HT 13 means you resist a normal poison 74.1% of the time and a minor NPC have a HT 13 means they fail 100% of the time, then normal poisons are already really scary. It makes resisted spells suddenly much more potent as crowd-clearers, as all you need to do to wipe out a mass of foes with Mass Sleep or lull them with Mass Suggestion or send they fleeing with Panic is to make your roll - no worry about margins, just succeed and these lesser mortals will succumb.
Or you can use it to simply speed up play - minor foes just wilt under supernatural attack, flee scary challenges, melt before your withering stare, fall like ragdolls under your incapacitating magic. You - and the big, important foes - get to resist.
And for the genre it's pulled from - running, say, GURPS Conan - it's pretty much how it works in the stories. Conan resists the poison. Conan breaks free from the jaws of the foe. Conan shrugs off the magic. Or, rarely, he doesn't, setting up more adventure later. It's not assured, but it is pretty much assured the nameless types all succumb. It's a very in-genre thing, and probably a superior implementation than giving bonuses or penalties just from the perspective of ease and speed.