A few observations I made over the last days that might be useful to some.
When creating a river system for a West Marches game, there will likely be a lot going back and forth from a starting town, and there will be much more adventures taking place close to that starting town than further away from it.
The river that players are going to explore can't really be a river that is also a major trade route. It seems not very plausible that you would have large numbers of relatively easily accessible ruins filled with valuables right next to busy traffic. The starting town should be at the very edge of the sandbox, and at the end of the regular river traffic route.
I felt very uncertain about the scale of the river system I was making, as I was putting stuff more clustered together near the starting town, and more spread out the further away you go. But that resulted in adventures to more distant and higher level ruins being very long, and getting increasingly bigger numbers of random encounter checks along the way.
But I realized that this isn't that much an issue when you let higher level parties have access to faster boats. Paddling in a small canoe is not that fast, especially when you go against the current. They are likely the only thing that new characters can afford, and its not an issue when their adventures are short and close to home. Upgrading to faster boats can be a form of progression that makes journeys to more distant places much faster and more viable. It's like an early non-magical version of getting access to flying carpets and teleportation and such.
In BECMI D&D, a river boat has twice the speed of a canoe, and a sail boat twice as much again. (Though oddly, the river boat costs twice as much as the sail boat.) In 5th edition, there's the keelboat, rowboat, and sailing ship, but their speeds seem very unrealistically slow. (I think they should be double what's shown.) Upgrading to a faster boat should feel like a milestone, and I think they should be expensive because of it.
I do random encounter checks based on time, and not by distance traveled, and doubling the speed means cutting random encounter checks in half.
I also got another issue all of you could help me with: What would be good ways to distinguish settlements as they are getting smaller and more remote in regards to what services they offer?
NPCs with healing magic would tend to be found with the more powerful ones in the larger cities near the coast, where the big temples are, and less powerful the more out you go into the wilderness. Treatment for the more serious conditions becomes harder to come by as the party goes into more dangerous areas, and might even force some PCs out of action for an adventure or two as they get passage from the forward base camp back to a bigger settlement closer to civilization.
The other thing would be shipyards. You can buy two new canoes in every settlement with some kind of market, but for a nice sailboat you need a larger town, and big cargo vessels could only be bought in the big ports at the coast.
I am considering the idea that the further you get from civilization, the worse the prices get that traders demand and pay. They have additional costs getting their goods, so their stuff is more expensive. And being the only trader in a hundred miles means their customers are unlikely to make a detour to get better prices somewhere else. But I'm not sure how to make that in an easy to handle calculation factor. (With XP for treasure, players should always get the full value of non-coin treasure, even if they can only sell it for less.) I guess a smaller inventory in heavy armor on the frontier would also make sense, as there's little demand. Unless someone where to have his armor destroyed by slimes 500 miles from the next armor smith.