settings

The biggest problem is likely complex variables in the variable table (nested arrays which become serialized). Here is a solution for changing only part of a complex variable: http://groups.drupal.org/node/52588#comment-144213 (if this doesn't work or is awkward, i have a similar solution that i can dig up, but i believe mine is less robust).

I think drupal_array_merge_deep() may be the function we want to use in these cases.

Update, there is an active real project doing much of this: http://drupal.org/project/variable

This is primarily a matter of deployment and developer sanity, but it is also a performance issue: large variables that aren't used on most pages shouldn't be loaded on every page.

The variable table has to change, and we need to distinguish variables that are needed on (most) every page load from those that clearly are not.

There does not seem to be any discussion about a file-based approach to saving configuration information in Drupal. Agaric comes to this conclusion after extensive Googling (see the keyword details of this post; by the way, I can confirm that word order matters when doing Google searches, even in the absence of quotation marks).