I've been a satisfied SB user for almost two years. IMHO, the NS/SB combination, if not 100% bullet-proof, is as close as we're going to get, at least as far as lightweight, low-knowledge solutions (unlike VMware, etc.) Sandboxie plays very nicely with NS. The only hitch is that since SB deletes *everything* when you empty the sandbox (which I have set to do every time I close the browser, although Alan has different preferences), any changes you make to your NS allow/forbid list, your AdBlock list, or any other, are also deleted (not saved). There is an easy config tweak to give SB permission to write those specific changes outside the sandbox, but I'm sure you'd rather figure that one out for yourself than have me tell you.
Sandboxie lets you boldly go where no man (or woman) should go.
Additional benefit: You can run *any* application sandboxed, not just browsers. For example, do you remember the recent critical vuln in Adobe 9, where opening a malicious .pdf could pwn you? I got rid of Adobe years ago, but if those pdfs were opened sandboxed, I think no harm could have resulted. Even Word docs have had critical vulns -- they can contain lots of executable code.
Installing SB gives you a new r-click context menu entry on any document or program, "Run Sandboxed". So you could d/l a movie, run with WinMediaPlayer or Apple QT inside the sandbox, without worrying about some sneaky code inside. (I won't run them any other way.)
Incidentally, alhtough even GM has suggested not to allow scripting at user-content sites like this one, I feel safe to allow it inside SB if I need it.
I browse sandboxed 100% of the time, and I think Alan is close to that, too. You need an unsandboxed, admin-privileged browser to get MS Updates, Fx and NS updates, etc., but that's about it. To d/l and install new sw, I d/l it into the sandboxed "desktop" (isolated from your real desktop, and created automatically when, e. g, you open Fx in SB). There you can scan it with your AV, poke at it, whatever, before moving it outside the sandbox. I get an automatic prompt when I d/l things, asking whether I would like to move it to my real desktop from the SB desktop, but that's a user choice.
Read the docs, try it, you'll like it. I'm no uber-geek, as I always warn people
but I have a lot of experience with SB, including some tweaking and config. Let me know if I can help you in any way.