I converted my '66 from a 352 and 3 speed OD to a 460/C6 combo - and I like it.
The conversion is NOT hard to do, and it is all FORD bolt up parts too! - PROVIDED three conditions are met:
1. You obtain the engine perches for the 460 from a 73 - 79 F-250
2. You obtain a complete 460 truck bracket and pulley set
3. You do this to a '65 or later Twin I-beam truck.

Here is my setup:

I am getting 15 MPG at 70 MPH with a nearly stock 460 in my '66 F-100. And I have power to spare.
‘86 460 bored 60 over with stock '86 heads - no porting
'77 F-250 460 engine perches and mounts
'69 straight up cam gears, Cloyes double roller with RV type cam
Edelbrock Performer (not RPM) intake and 1470 750 CFM carb on a 1" phenolic spacer
'76 Duraspark II ignition
Stock aftermarket manifolds with a 2 1/2 inch dual exhaust (plain mufflers); copper gaskets
'93 serpentine belt brackets and pulleys
'78 power steering pump, hoses with ’93 PS pulley
'76 power steering box
’76 power steering pitman arm
’92 power steering cooler, mounted in the frame
'70 steering column
'66 radiator (re-cored)
'66 alternator with '93 serpentine pulley and fan
'86 water pump
'86 fan clutch with '77 7-blade fan
'83 C-6 from an '83 F-350 fifth wheeler, with '77 C-6 linkage (internal shift rod and kickdown)
2.75 rear end
'83 stock rear sump oil pan, with stock oil pump, pickup tube and dipstick (includes main bearing bolt with stud to hold pickup in place)
Includes '93 A/C compressor, but A/C is not installed. (Needed for the serpentine belts.)
’76 F-150 3-inch rear brakes

The only modifications I had to make were:
Fabricate an accelerator cable bracket by combining an FE one with a 385 one.
Shorten the front driveshaft to adapt to the C-6 (with a conversion joint)
Change the C-6 internal shift linkage from a ’68 – ’79 C-6.
I used the '86 upper radiator hose on my original radiator, and it fit perfect once I cut one end short about 4 inches.