Something obviously happens to this game over time as far as I can tell.
I played about 40-45 hours with a single CTD. All of the southern desert, camps, vaults, different companions, etc. Even approached (but didn't enter) the strip.

after about the 45 hour mark I started getting regular crashes. Not too frequent, but probably on average once every hour or two.
Sometimes more frequent, sometimes less.

At one point steam detected 2 files had become corrupt so I let it redownload the entire game. This didn't fix anything. I've had crashes all over the place. Approaching caves, talking to random people, stepping out of buildings, etc.

I finished the game and since have started a new game, but the new game is far more unstable than the first game.
I've put in only a few hours (just gotten to nipton without much side questing), and I've crashed probably half a dozen times. I hadn't updated any drivers on my machine or changed direct X or anything else before this started.

This is getting tiresome. Tech support has been useless and from the looks of it isn't reply to anyone's emails at all.

I just sent a message now and their website states a response will happen within 48 hours.. I sent another request over a week ago that hasn't been answered.

System:
Windows 7 (fully updated)
Geforce 460 GTX 1 GB
4 GB Ram
Intel i760 @2.8Ghz

When it isn't crashing, the game runs very well.

Heck, I've even had the launcher crash twice on me.

yep it happened to me too.I have playing the game for about 20 hours and then every now and then it crashes.Thankfully the game autosaves regularly.Hopefully a patch will come up to fix all these crap.

Started happening to me at about 75 hours in. Was crashing about every half out or so and I've checked the thread for that. I've noticed that now it happens whenever my companion (Cass) starts shooting at enemies.

Great to see their immediate e-mail feature works as great as their tech support.
I wasn't notified of either of these replies by immediate email as I'd set. Perhaps that's the problem. We have such a huge delay for "immediate" here, who knows what they think 48 hours is. They must be using metric hours or something.

I thought it might have been a companion issue as well so I dumped all companions and did most of the game solo.

in the new game I haven't picked up a companion at all.

has anyone tried clearing their appdate directory for this game?
or removing old saves?

Can you guys tell me how many saves you approx had when the crashing started?

There are very few things this game does over time. One is storing temporary files the other would be storing saves. Little else changes. If something is happening over time it's got to be related to one of those two things.

I had 300 saves and over 50 hours before I finished the game. I only crashed 3 times.

I turned off all the auto-save functions and I think that helped me, but I've only done one game run-through so I don't that know for sure.

I also got the "2 files corrupt" info from Steam after I reinstalled the game (due to savegame problems, I lost everything...).

Anyway, one of the files was "Fallout_default.ini" in the "SteamApps\Common\fallout new vegas" folder. I had changed something there to have that change applied every time the Launcher re-detects the hardware settings.

The second one seems to be "InstallScript.vdf" also in the game dir. This is not relevant as it seems.