The game was running smooth the entire time until I got to Subway Town.

Some time after I got there and getting into missions there(distillery, vault etc.) I get random permanent framerate drops until I exit to wasteland. Sometimes when I quicksave and then quickload the framedrop disappears but most of the time that doesn't work...it's like the game is falling apart!

My PC:

4GB RAM 1600MHz DDR3
Windows 7 Ultimate x64
AMD Phenom II X2 550
ATI Radeon HD 5670 1GB

What are your ingame settings?

It doesn't matter, I set them lower and it still happens. Also on settings before the game was smooth the entire time, like I said. Also the framerate drop sometimes disappear if I quickload.

http://www.reading-skills-pyramid.org/comprehension.htm

Maybe something changed or updated in the system.
Try a restore point to a earlier time.
MY frame rated changed after the patch "dropped from 60 to 30fps"
I was running a config at the time of the patch. I removed the config & did a restore
got the patch & all was better. Still not completely right but better & back to 60fps.

Maybe try the ATi Catalyst 11.10 Preview 3 driver.

Maybe it works for you, because it works for me - although my case was different; a lower framerate all the time - but this one fixes it to a constant 60 for me.

dead link

I started the game today and everything is smooth again in every area, but it won't last...this new engine they made is really wacky.

after a few hours of break I started the game again and huge framerate drop everywhere again!

Does anyone have any idea why this is so random?

Oops sorry, just download the ATi Catalyst 11.10 Preview 3 driver - it's pretty much the same thing (excep this was just a single DLL file instead of the whole driver) instead.
I thought nobody ever downloaded the file, so I decided to delete it again.