Instead of archery there would be guns, motorcycles/cars replace horses/carts, rural settings will be more fantasy while towns/cities are concrete jungles. There could be "Oblivion gate" type portals instead of rural areas that give access to a fantasy dimension and possibly connect different sections of town through them. That would allow them to double land area while keeping the same size map.
Enemies would have resistance to different weapon types like regenerating foes would require a scattergun, or flamethrower from the gun category, a nice axe to chop off hunks and to bleed them out, or spells like freezing and burning which. Have enemies wearing insulated gear that protects against heat and cold magic but get cut down by physical weapons. Stuff like that.
Someone should make a game like that anyway. It is probably too ambitious of an idea... /cry