On the one hand, I run campaigns rather than games. I change the rules to match the setting and emphasize the things my group finds fun. I can't imagine doing it any other way.
On the other hand, players have certain expectations of what the rules will be when we sit down to play D&D, so I feel I have a certain obligation to adhere to the rules as written as much as possible when we play D&D. So if I'm planning to use a setting that doesn't correspond well to the core rules assumptions, I use a different ruleset as the base - sometimes an OGL game like AU or Conan, and sometimes a different ruleset like Chaosium's Basic Role-Playing.
On the other hand, players have certain expectations of what the rules will be when we sit down to play D&D, so I feel I have a certain obligation to adhere to the rules as written as much as possible when we play D&D. So if I'm planning to use a setting that doesn't correspond well to the core rules assumptions, I use a different ruleset as the base - sometimes an OGL game like AU or Conan, and sometimes a different ruleset like Chaosium's Basic Role-Playing.