Smczim: Cannot speak much to the TX and LA sections, but in my experience, from the Pearl River entrance (on the MS / LA border) to Appalachicola Bay, you can choose to run in fairly protected waters that are well charted. At the eastern end of St. George Island, a place informally known as Eastpoint, you'll have to emerge from protected waters into the open Gulf of Mexico. Depending on where you are bound in Florida, you may decide whether to cut straight across the Gulf to your destination or, instead, to more-or-less follow the two-fathom curve around Florida's "Big Bend." Either way, choose your weather and you'll have little trouble.
Whenever the weather permits, I stay inside until Eastpoint, then motor straight for the north end of Anclote Key, just off of Tarpon Springs. There you can re-enter the protected ICW route, if you like. Otherwise, if the Gulf is calm, just keep on running south along the Florida coastline, staying outside until reaching your destination. Most of the passes along the west coat of Florida are well marked, well-charted and easily navigated under normal conditions, no matter the state of the local tides.
I do recommend staying inside from Panama City / St. Andrew's Bay to Appalachicola. The outside stretch, from the St. Andrew's Bay entrance to Cape San Blas, has always seemed kind of miserable, with an annoyingly strong swell right on the beam.