Original settings in RPG game

[Serus]

Caves of Qud

From Steam:

Spoiler

Caves of Qud is a science fantasy roguelike epic steeped in retrofuturism, deep simulation, and swathes of sentient plants. Come inhabit an exotic world and chisel through layers of thousand-year-old civilizations. Decide: is it a dying earth, or is it on the verge of rebirth?
Who are you?
Play the role of a mutant indigenous to the salt-spangled dunes and jungles of Qud, or play a pure-strain descendant from one of the few remaining eco-domes—the toxic arboreta of Ekuemekiyye, the Holy City; the ice-sheathed arcology of Ibul; or the crustal mortars of Yawningmoon.

You arrive at the oasis-hamlet of Joppa, along the far rim of Moghra'yi, the Great Salt Desert. All around you, moisture farmers tend to groves of viridian watervine. There are huts wrought from rock salt and brinestalk. On the horizon, Qud's jungles strangle chrome steeples and rusted archways to the earth. Further and beyond, the fabled Spindle rises above the fray and pierces the cloud-ribboned sky.

You clutch your rifle, or your vibroblade, or your tattered scroll, or your poisonous stinger, or your hypnotized goat. You approach a watervine farmer—he lifts the brim of his straw hat and says, "Live and drink, friend."

Funnily enough if you disable permadeath in the options, CoQ can be played as a normal CRPG instead of a Roguelike and it's actually pretty good at it.

The locations are all interesting, and the setting absolutely menaces with atmosphere. It has a pretty fun main quest, a few good side quests, and the random generated ones aren't that bad because the content they send you into is at least randomly generated itself. Even if you turn permadeath off, the game is still pretty damn hard and you still need to actually know how to build characters in it to be able to finish the game without some extreme save scumming.

It's just a pity that the devs all have soy milk in their coffee.

If roguelikes or roguelikish games count then there are many that explore settings completely not known in the CRPG world. For example Unreal World - game set in Iron Age Finland (sic).

Edit: corrected an embarrassing typo.