Assuming you are targeting redfish, we have two distinct types of fishing, grass fishing on high flood tides, and then pretty much everything else. For the flood tide fishing, everyone seems to have their own secret pattern, but in general flies like the Dupree Spoon Fly, Turkey in the Grass (or Fiddler in the Straw) which are basically bendback style flies, and small crab patterns all seem to work, they just need to be weedless.
For the other times, and the majority of us (I believe) fish around the low tide part of the day, you really can't go wrong with a Clouser Minnow....I prefer Grey, others like Black or Chartreuse. Other patterns that I like include the Puglisi Perfect Minnow, Dorsey Kwan, and for top water action, the Gartside Gurgler....or a variation on that theme.
Go to the Black Fly and ask Randy, James, or Vaughn, they'll give you an idea on what the "hot" pattern of the day is.....enjoy.