Best practice is to establish your theme before starting design, but if made after the site has been designed or you are changing the them, then you have a new set of rules.
Typically, all selectors will change with the update to the Theme Panel unless modifications were to their style uniquely on an instance by instance basis. If you see an * next to the selectors type (i.e. H1*) indicates it was modified or never set to begin with, and these will not be affected site wide by making changes to Theme Panel.
So, establishing the typical selectors and staying true to the theme has allowed me to make site-wide changes effectively.