I had a 64 American with a 396/425hp Big Block Chevy and Muncie 4 speed, Mustang 9 inch rear. Only real issue was steering shaft too close to the number three exhaust. Rear end bolted right in.
Also had a 64 American wagon with a 350 Chevy and 350 turbo trans, Ford rear.
Motor mounts were not too much trouble, rear crossmember easy, rear bolted right in. Had under dash AC, Chevy compressor, custom hoses. Radiator in both were Ford because that is what I had. Bottom hose has to cross over as Ford and Chevy lower hoses connect on opposite sides.
Drove the wagon 6-7 years, untold miles no problem. Pretty quick in the light car, set up with Q Jet got 21 and change driving from NC to LA and back.
No big changes under the hood except to make the motor mounts but they were easy, SBC cast iron exhaust went right in. Real fun car. My wife loved it.