I have been lucky enough to race on a few of the great custom bikes. here are soe of my impressions
-Della Santa that was painted as a LeMond.
-Serrotta's steel/carbon (training bike) and Ti/carbon (race bike when I raced for Sierra Nevada Professional cycling team.
- Kelly bikes for cyclocross one year.
- and Now I get to race on a Rock Lobster.
http://rocklobstershop.blogspot.com/
I have to say that I was terribly disappointed with the Serrotta's, after going through their fit system my bikes ended up being way to tall and could not make a turn at speed, It was a dangerous bike. ( I have been racing since 1978, so I kind of know what I am doing

). They were not flexible in making the bike any different for me...I thought is this really custom if the builder is this rigid? I mean the bike could not turn at speed!
The Kelly's always had something "irregular" about them...like 133mm rear spacing...Chris Kelly would call that art...hmmmm. (makes putting a wheel in a bit difficult, a road bike is 130mm and a mountain bike is 135mm)
Della Santa was awesome. precision, speed and art all wrapped up into one, I wish I still had that bike.
Rock Lobster. AWESOME... Paul Sadoff is a true craftsman. In addition to being a frame builder, he also teaches a class at United Bicycle Institute on frame building. He is the man
I guess my point is, find the right builder for you for custom, and pay attention to the little things, not the pretty things. Fancy lugs and swooping tubes dont do you a lot of good in the bike gets fork chatter and handles like crap. Especially if you are going to carry panniers, a lot of these frame builders have never ridden a bike with bags on it...
just my $.02