This is a very complicated subject and I have hesitated to post much. However, after 170 hours of play, 850 saves and an untold number of crashes, I have found what works for me. I hope it might point you in the right direction.

First, I never had a crash in an inside cell. Even with large spaces and tons of enemies.
Second there were two places that reliably caused crashes: Moving from the Hoover Dam spawn point in almost any direction but particularly down the road across the dam toward the Legion; and entering the section of The Strip containing the Lucky 38.

Apart from the above, crashes usually occurred in open spaces with large expanses of sky. (I tried turning down the Water Effects as suggested, with little to no effect.) Sometimes I could avoid a crash by looking at the ground or walking backward into a new cell. Usually it would stutter and crash as background loading was occurring, but often there was no stutter—just a crash.

The only adjustments that seemed to have any effect at all were AA (Anti-Aliasing,) and Light & Specularity Fade. Running in Low didn't improve much from there.

Then I started looking at outside programs and this is where I got the idea that Steam might be playing a role. Anything that was using the Internet was playing havoc (pun intended) with the game—even my browser.

Closing the browser made the game much more stable, to the point that i could actually get some game time in. The final piece of the puzzle for me was a proprietary program that runs in the background; allowing formatted printing to the local machine from a web app. Unloading that has made the game function normally. I can now run on Ultra (except for AA) with only an occasional CTD.

While I realize that the specific program I have isn't relevant to anyone else, the concept is valid. There are tons of programs that sit quietly in the background communicating over the net. I have become jaded since the early days where almost no game would run with any background apps running. It was often necessary to call up Task Manager before every game session.

Now i know that FONV has absolutely no connection to the Internet. That leaves the only suspect: Steam. And you can't turn that off.

It looks like the old days are back.