Just take it out to the range and have fun shooting it for awhile. See what you like and don't like. As far as cosmetics go...I've seen a few Defenders with the Chip McCormick double diamond checkered rosewood grips. They look great. The Defender is a sharp little Colt 45.
If you've got the newer one, I'd recommend the Wilson Drop-in beavertail grip safety. No mods to the gun, though you might have to fit the trigger engagement area.
Everything else is personal taste of course.
(sights, safety, grips, mainspring housing)