There are lots of routes in the Dakotas going out with 40-60 stops, and 250-350 miles. Once in a while, you'll see a route with 30 stops, and 300 miles. Some of them end up 80 or 90 miles from the center at their furthest point. Those routes do nothing but bleed money, and I can see the appeal of dropping service from entire areas twice a week.
But I think there's a few problems that would keep that from being successful: (1) perishable food and medicine, (2) most of those package cars are really small, and can't hold two days worth of volume, (3) you're going to end up with 13 1/2 hour days following the days off.
A better approach would be to cut off specific stops, rather than whole zip codes. There are days that getting rid of four stops can shave off 30 miles. Do that enough places, and three routes traveling in a particular direction become two. But that approach would only work if local supervisors/dispatchers were trusted (and empowered) to do their jobs.