I pull a big toyhauler fiver as well (3200lbs of pin weight dry according the manufacture). I use a DRW f-350 with the tow boss package (4:30 gears and a rear sway bar). I can't speak to what tuning you should run as I use a Spartan (I usually run their 210 tow performance tune). I run 60 PSI in the rears just like the door sticker says (remember I've got 17 inch f-350 wheels, not the 19.5 inch one the 450 come with) and never had any issues and the tires are wearing fine. I pulled with stock rear suspension for probably 5k miles or so with no issues other than the truck was very slightly lower in the back (the factory contact overload springs were in use with trailer hooked up and my truck is a 4X4 that sits pretty level unloaded with all stock suspension). I have since put a set of firestone airbags on the back which allow me to push the rear end back up off the contact overload springs. So now the truck sits perfectly level. And I have since put about another 5k miles on it with the airbags. No real change in towing characteristics or safety as far as I can tell and the ride seems rougher now (same trailer, going over the same roads). I would do a least a few trips before putting on the airbags (you sure as hell aren't going to overload that f-450) and see how it does and if the truck sits level or low in the rear.
As for trailer brake controller setting, that’s mostly driver preference and will change based off how good the trailers brakes are. I usually run mine on 6 which is comfortable for my setup (three axel toyhauler with brakes on all three axels).
Fuel mileage, don't be expecting much, I usually run around 10 mpg on flat land and it gets worse if the throw some hills in the mix (although it tows like a beast uphill, it just sucks down the fuel while doing it).
On another note, how are you even able to get an 8 inch lifted truck under your toyhauler, did you lift it too?