If you have more than 1000 Bitcoins in your wallet:
1. get yourself a low cost netbook.
2. Install not bloated linux (like archlinux) or FreeBSD or OpenBSD (in order of growing paranoia).
- make sure that the above is done with ecrypted partitions and swap (plenty of guides on the net).
- make sure that the above is done while offline as much as possible (for truly paranoid ones).
- make sure that you do not not even configure wireless hardware, let alone using it
- physically plug in Ethernet cable when you need connectivity for a minute or so
3. Install bitcoin client, generate a bunch of bitcoin addresses (current account)
4. Over time transfer in small amounts your funds from your existing client to the addresses created in step 3
5. Keep this used exclusively as bitcoin client and nothing else, plug in Ethernet cable when you need to transfer money.
6. Keep this hardware wallet safe.
7. Creating a bitcoin savings account and making secure backups is still need to be done as described in multiply guides elsewhere.
P.S. Do not forget your passwords.
Is all of that really needed? Seriously? I mean what do you think they are going to do to if you don't install any malicious software or run software that hasn't been updated, or an OS that hasn't been updated for that matter.
Although the paranoia is understandable, if I had that many BitCoins in my account with the current exchange rate, I'd probably be extremely cautious too.
Also I saw another post that I forgot to quote about not having an anti-virus program and still never getting a virus, and people were saying I doubt it? How do you think viruses are aquired? Most of the time it's through blatent user error, such as running some random Java applet on a website, or not having your PDF reader updated, or turning off Windows Updates! Maybe you get attacked by the one in a million buffer overflow exploits before they are patched quickly enough, but aren't you running Windows 7 which has protection against it?

The best potential anti-virus is the person using the computer! Come on people, you just don't get exploited by clicking a link any more, we're well past the IE6 times!

I will make an important point though for people who aren't as paranoid but do want to keep themselves free of malicious software, simply keep everything updated and really limit what you download software-wise. Make sure Windows Updates are on, turning them off is a deathwish. Also on another note, try not to use many addons on browsers, addons are a bigger source of holes than the browsers themselves, one of the most commonly attacked one is Adobe PDF reader plugin, where you can literally get exploited just by browsing to a PDF on your browser, I'd avoid those kind of addons completely.