I believe the key to making this all work for you is doing your research. You no doubt have a set goal in mind, something that has power and able to cruise at highway speeds with good gas mileage. It is possible to come up with a combination that meet most of these goals but your may need to compromise on some things as well. If you are set on using the 6 speed trans you will definitely need the lower geared rear end (4.56 would be a good starting point) the easiest compromise would be the cam shaft.
As an example: I am building my truck not as a daily driver but a Hot Rod, something that will see a lot of traffic light to traffic light and drag strip use. The compromise for me is the rear end gearing, a higher gear so that I can drive it on the highway occasionally. A good work around would also have been a 5 speed, that would have allowed me to use a lower gear and still drive it at highway speeds. I chose the 4 speed for other reasons, 1) it's COOL, 2) I had it already, 3) it was given to me by a family member that has since passed on. (we all have our reasons)
As Jerry has said it wouldn't take long to swap out the cam and replace it with the correct cam for your needs. Cam shaft changes are fairly routine with racers as they look for the right balance of performance. I think at this point the cam swap is your best route. Contact a reputable company (comp Cams, Crane...) and talk with one of their Tech Reps. Explain your needs and ask what cam the would recommend. It is very possible to have a setup that gets close to your original plan.
