Blue
Ravenous Bugblatter Beast of Traal
If your campaign world had a different take on the pantheon, how do you handle the cleric class? If there are no gods, then logically there would be no clerics, possibly no paladins. Some players really like these classes but where do you draw a line between a campaign world with a certain story element and what is printed/RAW in the game manuals?
Well, Dark Sun took out all clerics back when it was first introduced. Having mechanics that support and enforce a setting gives your campaign a unique feel.
Alternately, just reskin. Divine magic is just divine magic becuase it says "divine" on the tin. Pretty much true for Arcane magic as well. The only class that has mechanical hooks into specific non-mundane power sources is the warlock. And even there it's easy to keep the sources and reskin them.
Perhaps there is more than one flavor of arcane magic. Perhaps people's beliefs in a shared ideal let them tap into that shared consciousness and make things happen. Perhaps just like sorcerers are natural talents, people's personalities can manifest power. Mayhaps there are organizations that train one in ways of doing things, just like monk monasteries, but don't have anything to do with religion and more with dueling philosophies.
In other words, figure what you want to happen, and then how to you explain it within your campaign.