I have done both. In fact, they were very similar builds. Both engines have a +0.030 over bore, similar cams, 600 cfm Holley's, approx 9:1 compression, etc. The only real difference is the 352 got aluminum Edelbrock heads, and the 351W used the stock '78 LTD smog heads. The 352 is in my '62 Merc Monterey wagon, backed by a non-lock-up AOD and 3.6 rear axle. The 351W is in a '51 F-1, backed by a M5R2 5 spd, and 3.08 rear axle. Tire size is real similar between the two.
The '62 will pull down 15 mpg cruising at 65 mph. The '51 will also pull 15 mpg on the highway. You could argue 352 is the more efficient motor of the two since the wagon weighs a good 1000 lbs more than the little pickup. I think the wagon probably has better aerodynamics, but it probably isn't all that great of a difference.
That said, I also built a decent 300 6. Full length split header, Comp 270-H cam, Offy Dual-Port Intake and Holley 600 cfm carb, flat top slugs that brought the compression up to about 9:1. Backed by an AOD in a '83 Bullnose, it would pull a consistent 18 mpg down on the highway at that magic 65 mph mark.
If I was concerned about mileage, I sure as heck wouldn't build something around a C6. Great, durable transmission, but terribly inefficient. Manual transmission with overdrive would be the best way to go.
As JimNolan said, target a 1800 to 2000 rpm cruising range. Build as much compression into it as you can get away with, and cam it to have the torque peak in the 2200-2500 rpm range and be prepared for the thing to be out of wind around 4500 rpms. Optimize the build so you can maximize the area under the entire torque curve, and dial in you AFR's across the cruising range.