'65 V200 wagon with mostly '76 running gear and electrical, dual circuit brakes, sway bars: I put ~340K miles on a stock cast crank 225 Carter BBD Super Six with MSD 6A and Blaster coil, tweaked advance curve, A-833 overdrive, 3.23 rear end (the stock ratio for that trans). I always got about 25 mpg highway, and up to 27 mpg when I kept it under 55 mph on long trips (correcting for all of the above). I fooled around with plugs and gaps a lot and settled on NGK Platinum at 0.045" as the noticeably happiest setup. Going bigger gap didn't seem to help anything.
I was originally running the stock Mopar electronic ignition box and reluctor distributor, but my brother gave me a 6A so I put it on; a noticeable increase in power, and my gas mileage went up. That 6A has about 320K miles on it with no issues.
I met a retired Chrysler engineer who looked at my Valiant and said, "25 mpg, right?" He had worked on that cam design.
The machinist had screwed up the valve stem seals, so I had to rebuild the head at about 60K miles. This engine got a new cam timing chain set at about 225K miles. When I tore it down at 340K it had good compression and oil pressure; the machinist found less than 0.005" taper in the cylinders!
I ran various full synthetic oils from BiMart for about 150K miles, then got creative since I figured I would be rebuilding soon; I started mixing synthetic and petroleum in the engine but always at least 50% synthetic, and changed with a new filter @ 3-4K miles. I also ran top cylinder lubes of various brands in the gas for most of these 340K miles. Ethos (methylated vegetable oil) was noticeably the best top cylinder lube I used; the mpg went up and the engine got smoother somehow.
This '65 rusted out in 2015 after 50 years as a daily driver. All of the modified '65 parts are now transferred to a '64 V200 with no rust. This modified parts set was originally driven about 40K miles in a '76 Valiant that rusted out in '94. This 8.25" rear end has only had synthetic fluid changes since I put it in the '76 body! I keep a notebook and recorded every ounce of gas and mileage that went into all of these cars. I was doing energy efficiency projects in Oregon, Washington, Idaho, and Montana, and lived near Eugene.