When 3.0 was released, the changes to the rules had an impact on setting design that few have taken to their logical conclusion. There are several big things and many minor ones, including:

 

Resources that affect quality of life. Now magic items become much more common as making them is easier. As magic items do not decay, that means a Hammer and Anvil of Fabrication will be passed on for countless generations. They will become more common as time passes as more and more wealthy smiths (and their patrons) pay for their creation. Magic items that cast Create Food and Water, Remove Disease, Break Enchantment and such will be likely in most cities, allowing for more people and more productivity. Though the initial expense is very high, an item that uses Polymorph Any Object to make materials for the user out of soil will be in extreme demand (since mineral to mineral is permanent). And more of them will be made, especially when the price comes down due to feats that reduce item creation costs and derived spells of lower level. Those that can only transform X into Y should be at least 2 levels lower.

 

And then there is "the billion chickens" problem but that has to do with poor economic design in the DMG. There has been a few solutions in d20 supplements, most of which come up with their own, better, formulas for how much gear and other stuff is for sale in communities of X size.

 

Alignment is real and can be measured. They are forms of energy created on the outer planes and have an impact on the material plane (consider the Detect X spells and bane weapon quality). This can throw free will out the window, but that is the way the world works. The impact of this is variable and depends on how society views the different alignments.

 

Monsters with classes. Since kobolds have sorcerer as a favored class, should they not have a larger percentage of spellcasters in their population? If that is true, shouldn't they have more magic items, from potions to weapons? And that is just kobolds. Awakened trees and giant ants (with the Awaken Vermin spell) can gain class levels and they don't have hands. If monsters can gain levels, doesn't that make them much more of a threat, thus forcing humans to compensate with more adventurers? The end result is a race on who can get the most powerful (N)PCs and win the upcoming cataclysmic war. Which brings up another problem-

 

Epic monsters and their effects on the commoner population. If all the humans are killed when they are of low level just for standing in the way of an giant beetle, then how to any of them get to epic levels to kill the insect? They aren't the kind of monster that is kept on an island far out to sea because they are the 800 pound gorilla that goes where it wants to. Castles are pointless because they aren't worth the effort to build- they are massive "kill me" signs asking for dragon or megamonsters to come and eat the people. Cities should be more spread out to allow people a chance at escaping. Even a tidal wave of non-epic magic items don't mean squat to these creatures as their damage and energy resistances mean they can ignore the "little" people or eat them with impunity.

 

Monster spellcasters also have an advantage that was not theirs in previous editions- spell and magic item research. They can create their own spells and items, specialized to their needs (possibly in the form of new metamagic feats). Looking at some of the d20 magic supplements, there is a ton of potential in new kinds of spells and spellcasting. I did this with sahuagen a few months ago and in all the issues of d Infinity and I hope that readers will take the idea and run with it.

 

And then there is the biosphere. There are two major sources of alien life in a setting- wizard creations and Gate spells. Both are going to have a major impact on natural life forms, usually mowing them over but possibly joining them in some forms of symbiosis. I consider the biosphere of Gamma World/Mutant Future to be a wonderous head ache because of all the interactions of mutants- this is as bad, if not worse. Xorn preying on deer for their bones results in local extinction, extremely paranoid deer, deer that learn to sleep on logs and never stand to graze or weird, magic deer- the creation of a local wizard who doesn't want to see the deer disappear.

 

And that is the major stuff I can think of. Minor stuff are legion- from individual spells (why isn't there a Continual Flame in every house and on every street?) to class features and racial traits to skill uses. Each and every one should have an impact on a setting, even if it is a small impact.

 

So what are the solutions to these issues? There is only two I can think of. One is to tinker with the world laws. Epic monsters simply can not exist but that also blocks human advancement. Alignment is energy but has no effect on those of the material plane, so the spells only affect outsiders. And so on. The other solution is divine intervention. A god says that no epic beetles are allowed in the nations of his followers- they simply explode or fade away if they wander into such a land. Spells of X domain or school are weakened or banned outright. And so on. This allows more of a patchwork setting- one should really know where one is, otherwise divine laws may bite one in the rear. But it also allows for epic beetles, the PCs just have to go where they can exist to fight them.