Ok I'm a lil confused;
I'm not being a smartazz when I say;
your 414 with a 251* cam, in a pick-up truck, will be spinning about 3300 at 65 mph:
and you are looking for 15 mpgs with a Predator?
I'll be waiting right here to see how that plays out.
Ok wait, maybe just a lil smartypants crept in there.
I know nothing about the Predator, but I hope she's is a pretty good mixer with the throttles nearly closed, and, you will have to mod the VA out to at least 20/24 degrees, to run close to 56* hiway timing, with that tight .025 squish. I highly recommend you get a dash-mounted, dial-back, electronic timing module so you can change the cruize timing on the fly; this will save you weeks of testing.
Ima thinking that combo will want full-time manifold vacuum to the VA.
But if the PowerTiming is locked at 36* and you add 24 VA at idle; that's 50 stinking degrees!
I don't think the engine will like that..... so now, Ima thinking to get rid of the locked out distributor.
Whatever you do, you are probably gonna be the pioneer so Best of "luck" to you.