As long as your calibration files are inline to run either E85 and Gasoline/ any mixture of the two you would be fine. But What
@MrBalll is saying, is that unless your going for an all out steet/track vehicle, it really isnt needed until youve done everything else and your looking for max power, with daily driving, it would be kinda negligible because you get worse fuel economy.
In the long run, E85 is more expensive. "IF" it costs you $3700 dollars for the whole year to use unleaded, it may end up costing "close" to double that for E85, because mileage goes out the window.
Port and polish, your choice really, but what mods are you gonna do to take advantage of it? I think stock compression on a 5.3 is 9.5, so if you mill .036 off the heads (862 if thats what they are ) and depending on gasket, you would be close to 10.5. At that CR and above, it will be beneficial to run 91+ or E-85.
If your going to go that route, might as well do exhaust. Stock is 2.75 so you might as well step up to a 3.
If going header, go longtubes over shorts.