The problem with making things harder in any other way than truly changing the type of challenge that is in front of the player is that the tools to deal with situations are not all that vast. You have buffs, debuffs, mitigation, crowd control and damage..that's really it. Players will always be at an advantage unless you pay for a ridiculously horrendous Ai system that can out think the player. Most games don't have that, so they do what they can to disadvantage the player. They make the enemies do way more damage, have more resistance and access to better gear..but act stupidly. The problem with this and mods that increase difficulty by ramping up numbers or even trying to level the playing field is that you completely eradicate the one major component the game has going for it, variety. Right now, you don't HAVE to play a certain way to win, if you make it very difficult with numbers then you would have to do certain things to win. Make resistance or WP too high then you have to have a class with a debuff to resistances, make poison heal enemies so much then you force players to stay out of melee..you may think its tactical, most people will find this kind of play repetitive and boring because the combat becomes formulaic and methodical.
A die in one hit scenario would be horrible for an RPG, it's just not set up for it..at all.
I think what you truly need is more skills that do more interesting things, most of the skills repeat themselves in other forms..fast track = wildfire, invisibility = hide in shadows, damage is damage then the AI for the enemies needs to get much smarter, it needs more variance and logic. The enemies need to understand when lightning strike is better than blitz bolt, when ricochet is meaningless and a basic attack is better etc. Honestly anything other than teaching the enemies how to fight better is simply glossing over numbers and pretending its harder when its not..its narrowing the necessary skill set, forcing players to play a certain way and beefing up the enemies with numbers to compensate for the lack of intelligence.