Biggest improvement you can make, power and mileage wise, is to increase the compression ratio. The more you squeeze the charge, the more efficient it becomes. However, the ratio you choose is also going to depend on the camshaft you want to use as well. The cam will determine the power band range, then you build teh compression ratio to match the duration of the cam.
With that, decent mileage figures and high torque vaues will still be possible. I'd recommned you chase maximum torque in the range you drive in rather than get too hung up on horsepower numbers. An engines torque peak is also its volumetric efficiency peak. So if you use too big of a cam and your max torque is at 5000 rpm, then your cruising miles per gallon will suffer, but you will have a lot of horsepower. By contrast, if your torque peak is under 3000 rpm, then you get massive amounts of torque down low in the range you normally drive in, but will give up some horsepower on the top end.
FWIW, the 440 in my truck gets almost 20 mpg and can pull a load like a diesel using this approach. But, it is running out of power overrpm.