1964-66 C40 454 Swap? School me please.

[Pick121]

Welcome to Heavy Haulers!
First comment is, no matter what engine or trans you are running, if you are keeping the original 2sp rear end you will likely run into higher RPM at highway speed issues. They are just not geared to cruise at 65-75mph, something to think about.
As for a BBC V8 mating to a V6 or I6 bell housing, I am pretty sure they will not be a plug & play, others who know for sure can chime in. So, might as well do the engine and trans together. These trucks came with SBC and BBC V8 options so, as long as you get the right engine mounts you should have no problems.
Good idea to upgrade the brakes, the main point of danger is the single pot master cylinder. Good to upgrade to 2 pot MC