Replacing an automatic transmission with a manual transmission. Is it worth it?

I don't think there's enough information to give you an answer. You'll have to consider the cost of the truck, the cost to replace the transmission, and how new of a model of truck. One thing to consider is that in many newer cars, the automatic and manual transmissions have virtually identical mileage - the computers are getting more efficient.

In a used truck, it might be worth looking for one with a damaged transmission with the full intention of replacing it. Major required repairs often reduce the value of a vehicle MORE than the repair will cost, so it could actually save you money - particularly as a manual transmission costs less than an auto.

Nowadays the transmission has sensors and computer controlled parts inside, so you would also have to change the ECM and all related wiring, just to save a little gas. It'll be easier to keep looking for your truck with a standard tranny.