The first thing I do is to change the strings and get it set up properly. I'm usually able to do it fairly well myself, but If need be I'll take it to a pro. Then I play the guitar stock for some time, typically at least half a year. I adjust the pickup height to see how that affects the tone and volume and try to figure out how to make the guitar sound as good as possible without messing with it.
The only things I have really felt the need to change in any of my guitars are the pickups, and in one instance the toggle switch. And quite frankly, only one of the pickup changes I have made has been done because I couldn't make the stock pup sound good to my ears (a 490T in my Faded Special SG was pulled out in favor of a '57 Classic+).
I've changed the pups in three of my guitars; The Derek Trucks SG, The aforementioned Special and in my Epi Dot. The DT got a Bare Knuckle PG Blues set that was really meant for a Les Paul Studio. I sold the Studio and put the pups in the DT for fun. I loved the result so much I decided to leave them in there. I dig the '57 Classics that were in there originally too, but decided to put them in my black SG instead. Now I have THREE awesome SGs... (Actually five, because the Epi '61 Special 50th Anniversary and the Gibson SG II both sound pretty nice as well.) The Dot was fine with the stock humbuckers, but I wanted some more p90-ish sounds, so it got a pair of Phat Cats.
When it comes to looks, I have added a pickguard to the DT and changed the trc and knobs on the Faded Special. Small things that don't matter when it comes to tone, but I like playing a guitar that I find visually pleasing.
I guess some guys here might find it sacrilegious to mod an already great guitar in a way that is irreversible (like the pickard on the DT, where the screw holes probably lowers the potential re-sale value). But quite frankly, I don't care about the value. I want guitars I can play, not sell. Now, I wouldn't mess with a perfectly functional 1961 SG or a 1959 Les Paul (as if I'll ever own a guitar like that), but modding can be fun. A lot of the time I suppose it really isn't necessary, but what the heck?