Start with the biggest tune that is safe for your truck then go for a nice drive and log it.
For cruse speed you want about 3-6 psi of boost anymore and MPG sux any less it sux.
For in the city driving just drive nice and smooth. Take out all the crap you dont need in the truck too.
That is what I do most of the time and I have seen 25.7MPG on the highways and a avg of 21.3 over all. But it is hard to be nice so most of the time I avg 18-20.