A set up with two toms mounted to the left of the bass drum, like the purple Fibes kit, is hard for me to play with a traditional grip. The back of my left hand stick wants to hit the hihat when I go to strike the small tom on the left. Then if I put two toms on the bass drum my ride cymbal is way to high or too far to the right. It's much easier on my body to have one up and either one or two down.
My current gig dictates my setup. I'm doing the huge drum sound thing, and my massive kick makes even one rack tom cumbersome.
If I were doing the more conventional things I used to (classic rock, R&B, Motown, etc) I'd go to a 2 up, 2 down setup consisting of 10" & 12" racks and 14" and 16" floors, although I'd have those in "rack tom" depths on a stand. When I played with 2 up, I had them on a stand centered in front of the snare. It was very ergonomic because I had the hats directly to the left of the snare, with the ride low and occupying the space between the 2nd rack tom and floor tom. I also had my primary crash on the tom stand directly above the racks.
Even after I finish the gig I'm doing now, I plan to keep using big bass drums. I just love 'em... we'll see where my setup goes when that time comes. Not knowing is half the fun!