Indysteel has it right. Handbuilt custom wheels can be tuned to your riding style and offer a vastly different ride - whether you want it softer or harsher. Also, many of the pre-built wheel sets have wide spokes which are miserable in cross winds.

You may find that the tires you really like don't mount well on the rims because the tires are a bit undersized and the rims a bit oversized. I had a very unhappy experience with Michelin carbons and Ritchey rims once.

Handbuilt customs are easier to repair. Most shops will stock the spokes to get you back on the road and you can do some tensioning out on the road if neccessary.

Custom - you can pick the colors for rim, hub, nipples and spokes - just for fun.