What options for O/D behind a S/6?

The 6 cylinder vs. V8 mpg comparison is true. You really don't get a free lunch with a small engine. If you drive it with an egg under your foot, you'll get good mileage. If you drive it in order to keep up with modern traffic, you won't. There is just simply not enough power and you will be in the throttle so much your mileage will be out the window.

That's like a buddy that had one of the first Nissan frontier trucks, a 1998 Xtra cab 4wd with a 4cyl. Not only was it severely underpowered, but highway mileage was about 16mpg at 70 mpg, simply because it had to work so hard. With a 4cyl!

My suggestion would be to scrap the slant idea and put a V8 in it. You'll be quite happy with it.