Could be a storyline/mechanics cross-over, similar to how in PS:T the number of shadows in the negative plane fortress scales according to how many times TNO has (a) died and (b) given away his name, location or existence. Is justified in lore as turning people into shadows is how TNO's immortality works, and (b) in the lore is supposed to improve their ability to 'zero in' on him, i.e. giving them time to prepare for his assault.
I'm thinking that the power to reload could be presented as some awesome, virtually unseen means of massively altering the universe, even if it only alters the universe to the extent that it affects the player. Make it part of a player class/story, so he's some sort of plane-shifter or shape-shifter. Different kinds of shifter for different classes: so a fighter is a shape-shifter, able to control his own matter by shifting into different creatures and machines for different abilities. Thieving skills could work from a similar shifting mechanic - you're shifting into birds for stealth (but are obviously weaker at combat if spotted). An earth-shifter has nothing but basic fighting skills, but shifts the world around them, creating what we'd normally call 'magic' by shifting matter through sending fireballs, crushing opponents in chasms, and the air around them ultra-heavy so it traps/crushes them. A body-shifter is like a cleric/necromancer, affecting the bodies of others either to heal, or to curse (turn their hands into hooves, making them unable to use weapons), make them brain-dead zombies under your control or making them grow ultra-large or small, turning their blood to acid, etc.
Packed in with that is the ultimate shifting ability - the one that sets your character apart from the others - the ability to alter the world be reloading. BUT you learn early that this comes at a terrible cost. The first time you reload (you can't reload until this early point - with option to skip for later playthroughs) it kills your companion/family/mcguffin. The idea is that you're changing something that shouldn't be changed, and that people, and possible the world itself, dies a little each time you do it - i.e. you can sort of play with it, but you can't quite put things back 100% correctly, and someone is going to die each time, sometimes someone insignificant, but also sometimes someone who mattered to you.
Now later you get to have the big combat where the difficulty and number of opponents (lost souls, whatever) is determined by how many times you have reloaded.
But....HERE is the awesome bit (in my opinion). You aren't the ONLY guy in the world with the power to reload. Someone else - maybe a friend who discovers the secret with you, but unlike you thinks 'screw it - I don't care who dies for my immortality', maybe someone who doesn't know you other than that you're 'the other guy with that power'. But somewhere along the lines you'll find out that this other antagonist has the same power. Hints can be given like having souls come to steal the life of a character when you've actually avoided reloading to stop that happening. Or (if you're happy to go evil and say 'fuck the consequences') the discovery that something you've reloaded in order to steal no longer appears, no matter how many times you reload knowing it 'should' be there.
Later on, you discover that one of the 'bosses' you killed really is no longer dead - same turns out to apply for a few. But is that early boss the guy with the reload power? Or has the other 'reloader' just used reload to resurrect his minion, while throwing you off the scent? Is your game journal lying to you? As you go on, you'll find ways of keeping records that are immune to reloads - I'm envisaging a discovery of meta-worlds and fantasy names for what folk from a fantasy world would call 'hacking code' if they were to somehow discover its existence. You'd get a journal that kept accurate information, even if it didn't match your own experience of gameplay - so you'd go to kill someone, turns out they weren't home, but you looted their castle. But if you check your journal it says you killed them after an epic battle, someone then reloaded the world, warned them and they escaped before your get there.
Ok, that's sounding shit, but it's drunken ramblings so it isn't going to compare to a serious attempt at a gaming concept. Nonetheless, I think there's some awesome stuff you could play with using it. You could fit it right into that niche of 'self-knowing enough to be interesting' but 'not so pretentious that its head will rupture its colon'. I.e. the game would have to be good in its own right, even without the 'reload' bit. And you'd need good enough writing that it didn't seem like a gimic added for marketing press.
For me it's a flow-on from the old and sadly underused idea of having more active adventuring parties in the world - horray for Wiz7. But if they could do that with Wiz7, I'd have loved to see Van Buren's take on it (or was it Torn that had the idea of an opposing adventuring party as badass as your own?). For me, the ability to reload, restricted in-game by suitable lore and mechanics consequences, is a logical next step.