Recently came back to the game after playing it years ago and other than a few random crashes (maybe once in 8 hours of play) things were stable.

However this all changed when I reached the Blood & Wine expansion and specifically anywhere in the main city.

Sometimes it will crash almost instantly on entering, other times within 10-15 mins, this happens very consistently and doesn't seem to happen like this anywhere else in the game.

I'm a programmer so I thought I'd open the crash reports in WinDbg, and the thread with the exception always has calls to ntdll!RtlpDosPathNameToRelativeNtPathName and ntdll!RtlpAllocateHealInternal

These function calls are related to string processing, specifically file path processing. After a little bit of digging I noticed that the crashes could be lining up with when the game tried to autosave. So I just sat in the city and waited for the next crash and yes, it happened when the game should have done an autosave, though this time it was during a Gwent match which seemed a little weird as I wasn't aware the game autosaved during Gwent.

Anyway I forced the game to have an autosave time of 12 hours by manually setting it in the user settings and then making the user settings read only. Managed to play the rest of my session without a crash and went to bed.

This morning however it crashed within 1 min of loading in to the city so I'm back to square one and ready to give up.

Other things I've also tried without success is manually setting the TextureMemoryBudget to number higher than the default as I'd read another post that this fixed crashes in the city for someone else, but hasn't worked for me. Neither has trying the DX11 version.

I'm on Windows 10 and have done all the usual things such as update drivers, update Windows, verify game files, removed mods etc

I've just re-started the game after 4.04 (hadn't played in ages so I thought I'd give it a look) and found out that what triggered the crashes for me was the Nvidia hairworks. I knew I can run the game fine on my laptop with ultra settings, but the default for ultra and high are the hairworks turned on, which causes the game crash instantly for me.

I don't know if they've changed something with the drivers at Nvidia or in the game, but I remember that the last time I tried turning on Nvidia hairworks I could still play. Sure, there was a lag in performance here and there and my laptop sounded like it was about to take off, but I could play.

Not a big deal though, I don't like how Nvidia hairworks look like anyway.

See TLDR at bottom

After further testing I've managed to get a set of user settings that make the game stable on DX12 version. The test was to stand outside the Ducal Camerlingo office (the guy that pays you for killing bandit camps in Toussaint). Standing there my game normally crashes within 15mins and often within 5min.

Setting the graphics preset to 'Low' and turning off DLSS resulted in a stable game that didn't crash. I stopped the test after about 45min of just standing around in the usual crash spot.

I then increased the NPC background number setting from low to medium, in the setting .ini file this increases the spawn number from 75 to 100. Doing this resulted in the game crashing as normal. Ok I thought, there's probably some resource issue or leak that the devs haven't fixed yet related to number of NPCs. Just to test I put the NPC number back to low and again couldn't get it to crash.

At this point I turned the preset up to High (the setting I'd been playing the rest of the game on without issue) and turned DLSS back on but kept the NPC number still at low. It started off promising but eventually still did crash (though took longer).

The final test I've just done is to set the presets to Medium, DLSS on and the NPC background number at Low. Managed to stay in the crash spot without issue. It may have still crashed eventually but after 30m it felt fine. It's possible I could refine the options even more to get slightly better graphics without it crashing but at this point I can't be bothered.

Seems like there's some resource issue in the game that standing in the middle of Beauclair exposes.

TLDR:
If your game crashes mainly in cities try setting preset to Medium (it doesn't look all that bad) and NPC background number to Low. Having the Low preset is likely to be even more stable but game looks pretty bad at this point.