Most if not all settings have an item Reset to Default Value in the context menu. This would be helpful when tracking down issues when someone played a bit to much with the settings.
Could an addon be created to highlight changed settings, or would this require to change implementation of blender to adjust all hardcoded default values to the values of the default scene?
Can an hook-method be defined to intercept calls to draw an UI control so that the changed settings could be highlighted in one piece of code?
Apart from that there currently is a bug regarding the default settings.