With the right offset something along the lines of a 315 wide tire can be fit out back. Up front I fit 275/40R17 on my Isuzu RCSB without much trouble other than spacing the steering stops out from the control arm 1/4" to keep the tires from rubbing. That was on a 17x9 wheel with 0 offset. Again, with the right offset this could be improved upon, but I didn't try any spacers.
Ride height will have an effect on how well tires fit too. I didn't go lower than the factory 1.5" + another 0.5" from tall lower ball joints as I didn't want to push the roll center too low.
For a street setup I always suggest Xtreme/ZQ8 springs + tall lower ball joint, and fresh rubber control arm bushings with an offset crossshaft to help with alignment. I've run 0.5 camber, 5.5 caster, and slight toe in with that setup and been happy. A new ZQ8 steering box, a U joint to replace the rag joint in the steering shaft, and fresh steering linkage will really tighten everything up. To go lower a 2" spindle is the best option as any shorter of a spring really pushes the roll center low and control arms quickly run out of travel.
Next level would be a Tall Upper Ball Joint and a shorter Upper Control Arm. There are several Control Arm options out there UB machine, Speedway, Spohn, UMI, SPC, etc. Some are adjustable, some aren't.
Bolt in coil over kits are an option, but the shock and spring mounts aren't aligned perfectly on our trucks, so while they work some have had issues like worn out shocks or odd wear on the springs. QA1 only has spring rates up to 650lbs, which might not be enough. Rentedmule is fairly happy with his 550 on his extended cab from what I gather, but wouldn't mind a higher rate. I'll be trying 650 on my Blazer.
To the real extreme the spring mounts/cups could be cut out and the frame smoothed over to add a standard 2" coil over to the outside of the frame. Lots of room to improve over the stock spring and shock geometry with this and lots more spring and shock options.
With any of the setups comfort will most likely depend on the bushings you use. I stick with new rubber for the street, but with the Body on Frame design of a truck a stiffer bushing material could be used with out the severe harshness depending on your tolerance. Good sound deadening makes a difference in the perceived harshness too.
