'92 Engine Swap, Help????

I've got a '92 F-250 4X4 with a 460 ci. Engine metric (elec. 4 spd) transmission. I would like to know if I can swap the 460 ci for a 351 ci without any major problems? ie, are the same computer and wiring harness useable / direct swap?
Or, What can I do to lower the fuel consumption of the 460 ci? Right now I'm getting 12.5 mpg and the compression is 175 psi to 180 psi.
:uhoh:

The bolt pattern for the tranny is wrong. But, there are small block E4ODs. Computer and most electrical is different. You probably would never save in fuel what you would spend in a conversion.

Complete "Banks" exhaust helps(and you don't get manifold leaks too) Thats about 1 MPG better I got. But the power increase is awesome!

Change the gearing, that will make a pretty big difference. Most 250/350s got 4.10s, go with 3.55s and you should pick up about 1-2 mpg. It also really depends on how you drive, but gears will help regardless.