In working on my own campaign setting, and I am trying to come up with some unique twists.
Out of curiosity, do you wish to use unique twists upon the races, the general setting, the attitude toward adventurers, or what exactly? And how far do you wish to twist things?
For example, do you want elves to be a rarely seen legendary race - perhaps using steam punk but living beyond the mountains and maintaining a cultural Prime Directive to avoid contact with 'less advanced' races? Or perhaps halflings are the primary race in the world with gnomes taking the position of elves (ie: long lived, highly magical) and goblins taking the position of half-orcs (short-lived, barbarous), and humans being an uncommon giant race only recently encountered?
Or perhaps horses and sheep do not exist - with the result that races travel at generally slower rates, and llamas are used both for wool and to pull wagons and the occasional rickety chariot. Or perhaps horses are simply smaller - such that only small sized races can use them, with obvious benefits to them over larger sized races such as humans, elves, and even dwarves. Or are dwarves *just* small enough to use these smaller horses.
Maybe dwarves are genderless statues brought to life by a secret dwarven divine ritual, having traits similar to the warforged. Their deity determines how many of them exist, perhaps at times keeping their numbers low for his or her own unknown reasons.
Or maybe magic is more limited, such that ambient ley only allows for perhaps up to 2nd level spells, liquid ley (readily found in small pools at ley nexus points) must be carried about to allow for higher level spells (up to level 5 or 6), and rare ley stones (crystallized under unknown conditions in ley pools) are used for highest level spells. Ley might be a limited / limiting resource, such that only the lower level spells are commonly available. Perhaps all magic requires this ley, but divine magic also draws upon the power of the deity to supplement this, allowing divine casters to cast a level or two higher than arcane with the same ley supplies.
Or maybe iron is incredibly rare, such that the world is locked in the bronze age. Tin, needed for bronze (and in RL bronze ages far less common than copper), is considered as valuable as silver - maybe even being used in coinage in place of silver. Or maybe crystals form far more readily than in RL, with the result that crystal is a common material for an otherwise bronze or medieval setting: used in place of metals for coins, certain tools, etc. Gems are all a step less expensive (ie: precious treated as semi-precious, semi-precious treated as common, etc). Maybe crystal can even be grown to fill a mold, such that statues and forms of pottery are commonly made of crystal instead of terracotta.
Maybe adventurers are seen as foolish or even crazy for wandering the dangerous wilderness. Or worse .... perhaps all who die enter the ghostly ethereal plane, only to be claimed and taken by a celestial servant of their deity if their body is buried in consecrated ground. Perhaps each consecrated cemetery and necropolis has - on the 'other side' - one or more minor celestials whose only purpose is to transport souls of worshippers to their deity. Beyond these consecrated places the souls of any who die are doomed to wander until they go mad, are found and taken by fiends, or happen upon a celestial loyal to their deity but on some other task - and willing to transport them despite that other task. Thus every army likely has multiple priests present to guarantee any souls of the dead can be conducted from the battle field to the afterlife safely via summoning minor celestials or consecrating a burial ground so that the souls will be safe until they are collected by a celestial.
Or, if you really want to turn some ideas on end, perhaps the after life is more strongly divided between law and chaos than between good and evil. Devils and Archons work side by side against Demons and Azatas, differing in tactics against common foes.
