I'm currently designing a roguelike that aims to capture the high fantasy gameplay concepts and present them in a very different setting. This futuristic setting stars a world that is populated not by dragons and magic, but by machines and technology. Some concepts I've already envisioned in this new setting are:

• Mythical creatures such as dragons, giants, and other assorted monsters are now represented by a network of sentient, biomechanical entities
• Different humanoid races like orcs and elves are "modern" humans with biomechanical or mutant characteristics
• Magic is replaced with electromagnetic, nanotechnic, or chemical weapons and tools (possibly separating these disciplines?)
• Undead creatures are machines or cyborgs controlled by a necromancer, or hacker
• Potions are very similar, instead being injected rather than ingested
• Dungeons are abandoned underground facilities (including actual prisons)
• Melee weapons are relevant because armor technology has surpassed firearm technology
• Arrow and bolt weapons are railguns/coilguns; ammo is large but able to penetrate armor, unlike conventional bullets

Things I've picked out but haven't been able to translate yet:

• Treasure (chests)
• Deities and worship (maybe just keep this? but how would I explain the effects)
• A relatively small population and medieval social structure

If any of you guys could come up with ideas, especially for those concepts outlined at the bottom, it would be really helpful. Thanks!

• Treasure (chests) : Computers with datacaches that can contain ingame info, plot background, or downloadable 'patches' and 'mods' for your digital weaponry?
• Deities and worship : Replace 'deities' with charismatic CEOs, 'worship' with Apple fanboys, and organized religion with corporations? The effects are better biomods for those closer to the CEO.
• A relatively small population : Gene plagues, ftw.
• medieval social structure : The "fuedal system: serve the local baron, he owns all the land you live on" is replaced by the "corporate system: employed by the local corporation CEO."

Your bolt weapons sound like they'd kill or incapacitate in one hit. Then again, arrows do that as well, in real life, but not in games. Well, swords would kill or incapacitate in one hit IRL also - but games have conditioned us to 'twenty sword blows or thirty arrows to kill', but have also conditioned us to '3 gun shots to kill'. With current videogame conditioning, you'll have to fight against the immersion-break that a railgun won't just kill someone in one hit.

Hmm...the mega-corporation thing could work well, provided I don't come across as a complete libertarian bigot. Possibly the idea of corporations evolving into kingdoms?

Not only can I provide you with ideas, but I can recommend some games for you to play to see what's been done out there. Some of my favorites.

Mass Effect. I know the ending and the DLC release schedule both caught a lot of flack, even after the free DLC they released for it, but the experience was amazing, from start too finish. This game has a lot of attention for a reason. Play them.

Knights of the Old Republic. KOTOR is typically pretty inexpensive on Steam and similar services, and the MMORPG version is free-to-play...at least the part you're interested in (playing through as a character in an sci fantasy rpg). I really enjoyed KOTOR and for a few months after it launched I had a great time with the MMO.

Each of these games has large monsters and some reskinning of "magic" (Biotics and the Force) and fit your other criteria very well.

Thanks for the recommendations, but I'm not aiming to create this level of science fiction, and the games are quite dissimilar to the roguelike genre.

Perhaps I should have specified that I'm not aiming for full-blown galactic civilization science fiction. It's still high fantasy in terms of being set on a parallel Earth.

you could have a look at Warhammer 40000

Note that the best results (gameplay wise) you get when you structure something that can not be converted to another setting (like cyperspace and megacorporations in cyberpunk setting, constructing weird machines in steampunk, etc). But that's just a note.

A relatively small population and medieval social structure

Actually that one could work pretty well. I mean, everyone knows that Darth Vader was real, so if he was a lord it means there must have been some feudal structure :)