Your best mileage gain will be a overdrive trans. Also, if economy is important, dont use too big of a carb, it's just dumping unburned gas out the tailpipe. Use the carb size formula: The math formula is: CARB CFM = Cubic Inches x Max RPM's / 3456 x VE%

Max RPM's for a good street small block is probably around 6000. VE is Volumetric Efficency. A basic stock 350 is about 75% efficent while a well built small block can achieve 100%. Work it both ways and it'll give you idea of the range of sizes you're looking at. The goal is to completely burn the fuel as much as possible.