
I poke around in the Registry whenever I feel it is necessary. Earlier on in this repair story I did exactly as you suggest - cleaned the registry of all A/V entries. I'd had AVG, Kaspersky, and Avast! on the machine. Every one of them left tracks; which I cleaned.
Since I look for left-over directories and files after an uninstall (of any program) each time I uninstall, the only ones I found were Avast5 entries. So I deleted them.
The System File Checker has been run several times but in a couple of cases it found items that it "couldn't fix due to ..." The '...' means (I think) that it should have been run in Safe Mode (my mistake). I did this and they were repaired.
My defrag program of choice is Smart Defrag. Vista has its own version of defrag, but occasionally I run SD just to touch up things. My HDD is a 180G drive and is approximately 42% full. I have two batch files I use to either turn the hibernation file on or off.
I also know that System restore can get out of hand so I occasionally (when the computer is running okay) turn it off, do a HDD Cleanup, and turn it back on.
At the moment, my first priority is trying to find out why my system takes around 4 to 8 minutes to become fully operational. In a lot of cases, the desktop will appear, my icons will refresh, and then I get the whirling circle mouse pointer. It will stay that way for around two minutes. If I try to bring up the task bar (I have it auto-hidden), it will appear, and I get tool tips over all notification area icons except the network icon. If I try to launch ANY program, I get a whirling circle over the task bar that lasts for minutes while the HDD gets banged hard the whole time. It takes (if I don't do ANYTHING at all) around the aforementioned 8 minutes before the network icon will finally show the "blue ball' of Internet connectivity. I've replaced the drivers for the networking system a couple of times to no avail.
I realize this points to a whole lot more going on than just an A/V trying to update BUT before I took Avast! off the machine, everything would work perfectly just as soon as the Avast! pop-up informed me I was updated. Now, the system boots up quickly but will still occasionally hang as I've described. Once it gave me spinning circles for around 5 minutes and then the whole screen went opaque (greyed out) and the HDD LED stayed on. Something is definitely wrong here but I haven't laid my finger on it yet.