I have a standard setup I use for most waters, and, since I mostly nymph fish it is a nymph rig under an indicator. Since we can use three flies in Idaho I'll usually set up with a heavy "Big Ugly" Rubberlegs stonefly nymph, trailed by either a bead-head flashback Pheasant-tail nymph or one of my KG's South Fork Special nymphs, or an Improved Shop Vac nymph, trailed then by some type of midge offering such as a KG's Deep Purple Peril midge, a Rainbow Warrior or small Zebra Midge.
Here are some pics:
"Big Ugly" Rubberlegs:
Bead-head Flashback Pheasant-tail:
KG's South Fork Special:
KG's 'Improved' Shop Vac (original Shop Vac fly by Craig Matthews):
KG's Deep Purple Peril midge:
Can't say that I have a go-to 'fly', rather, a go-to setup of multiple flies whenever I fish unfamiliar water. Last year I fished the Big Horn River for the first time. As I was getting rigged up our host noticed what I was going to use and simply said "Won't work, no stoneflies in this river..." I was a bit surprised, but I paid attention and re-rigged my setup to what he suggested. My buddy who swears by the big rubberlegs nymphs refused to believe the fish wouldn't take his rubberlegs even in water without stoneflies and he went fishless for the day...