I had suspected this for a long time but didn't really have any proof, because I use sleep and ReadyBoost quite a bit. I had noticed that there seemed to be a hard drive frenzy when I would resume from sleep and that Vista was essentially rewriting all of my 4GB ReadyBoost cache file.
Well, it looks like I was right, but not for the reason I originally thought - it is due to the old ReadyBoost key becoming invalid and it does recreate the ReadyBoot.sfcache file.
You can read about it more
here, and it looks like the behavior will be changed in Vista SP1 so that sleeping your computer will not cause major drive thrashing on resume.
On a good note, my Seagate Momentus 7200.2 drive should be here this week for my laptop and the current Hitachi drive will moved to the SATA drive bay as a dedicated virtual machine repository. I won't have to worry about thrashing as much at that point.

The only bummer is that I will have to take out my secondary bay battery to use both hard drives at once. On the upside, I don't have to drag around a Firewire/USB external hard drive and power adapter anymore.
It looks like
Carl also noticed the same problem earlier this year.