Okay, I'm at a loss. I've installed New Vegas, put on some fairly standard mods that have always worked for me in the past. Nothing too heavy (Darn UI, I-Hud, Project Nevada, World of Pain and a whole bunch of texture updaters, 4GB Patch). Yet when I try to start New Game, it asks me if I want to overwrite Auto-save (important bit: i have no save games). i say Yes.... and nothing happens, I just go back to the menu.

I've tried verifing my game cache. it finds 1 or 2 files invalid, re-DLs, still nothing. I've uninstalled and reinstalled my UI mods. Still nothing. I've looked online. Nothing. This is... vexxing. Any suggestions?

Try deleting your .ini files (Fallout and FalloutPrefs, located in My Documents\My Games\Fallout NV) so the game has to generate a default set of ini files.

ETA - fixed file path.

Have you tried disabling all your mods? Uncheck them all except the DLC and disable archive invalidated. See what happens. If you can successfully start a game then it's a mod issue.

I eventually fixed this with the INI fix, as suggested above. Been running fine for a couple of days. Now onto a new problem (Mentioned in related thread.)

When you uninstall New Vegas (and Fallout 3), the .ini files don't get removed from your HDD. So when you decide later that you want to reinstall the games, they see the .ini files from your old installation and try to use those instead of generating a fresh set of default ones. Bad things can often happen.