I find that I am happiest if I leave my pants size the same. I tend to wear my clothes a bit loose, so you may have be different.
I have found the Milt Sparks VMII with a Sig P220 (single stack .45) to be incredible comfortable. Oddly enough, the all kydex Comp-Tac CTAC with a 9mm Baby Glock (26) is also very comfortable.
The leather/kydex Comp-Tac MTAC with a Glock 19 is acceptable, but not as form fitting as the Sparks.