Note: As the author of this post, I also authored a slight revision of this into the Official Homestead Documentation.

I think if you are looking for a combination of ease-of-use and very good security, then a Mist multisignature wallet is your best bet. The Ethereum Foundation has (and still is) putting hundreds of thousands of dollars into Mist and it's underlying components, so they are as safe, reliable, and secure as possible.

It's very easy to create / backup account files in Mist. In the 'Accounts' section click 'Add Account'. Pick a strong yet easy-to-remember password (remember there is no password recovery option), confirm it, and your account is created. Create at least 2 accounts. Then click 'Backup' in the top menu. Choose the 'keystore' folder, opposite-click on it / choose 'copy' (do NOT choose 'cut', that would be very bad). Navigate to your desktop, opposite-click in a blank area and choose 'paste'.

Now that you have copied your account keys, you can back them up. You may want to rename this new copy of the 'keystore' folder to something like 'Ethereum-keystore-backup-year-month-day' so you have quick recognition of it later. At this point you can then add the folder contents to a zip / rar file (and even password-protect the archive with another strong yet easy-to-remember password if backing up online), copy it to a USB Drive, burn it to a CD / DVD, or upload it to online storage (Dropbox / Google Drive / etc).

You now need to add approximately no less than 0.02 ETH to your primary account (the account you will initiate creation of a multisig wallet with). This is required for the transaction fee when you create the multisig wallet contract.

You will be entering the full addresses of all the accounts you are attaching to this multisig wallet, when you create it. I recommend copying / pasting each address into a plain text editor (notepad / kedit / etc), after going to each account's details page in Mist, and choosing 'copy address' from the right-side column of buttons.

We are now ready to create the multisig wallet. Under 'Wallet Contracts', select 'Add Wallet Contract'. Give it a name, select the primary account owner, and choose 'Multisignature Wallet Contract'. You will see something like this appear:

This is a joint account controlled by X owners. You can send up to X ether per day. Any transaction over that daily limit requires the confirmation of X owners.

Set whatever amount of owners (accounts) you are attaching to this multisig wallet, whatever you want for a daily withdrawal limit (that only requires one account to withdrawal that amount), and how many owners (accounts) are required to approve any withdrawal amount over the daily limit.

Now add the addresses of the accounts that you copied / pasted into your text editor earlier, confirm all your settings are correct, and click 'Create' at the bottom. You will then need to enter your password to send the transaction. In the 'Wallet Contracts' section it should show your new wallet, and say 'creating'.

When wallet creation is complete, you should see your contract address on the screen. Select the entire address, copy / paste it into a new text file in your text editor, and save the text file to your desktop as 'Ethereum-Wallet-Address.txt', or whatever you want to name it.

Now all you need to do is backup the 'Ethereum-Wallet-Address.txt' file the same way you backed up your account files, and then you are ready to load your new multisig wallet with ETH using this address.

If you are restoring from backup, simply copy the files inside the 'Ethereum-keystore-backup' folder over into the 'keystore' folder mentioned in the first section. FYI, you may need to create the 'keystore' folder if it's a brand new install of Mist on a machine it was never installed on before (the first time you create an account is when this folder is created). As for restoring a multisig wallet, instead of choosing 'Multisignature Wallet Contract' like we did before when creating it, we merely choose 'Import Wallet' instead.

Update: A couple folks I've talked to have had a few minor issues setting up Mist that are fairly easy fixes...

1) Mist won't sync. One solution that works well is syncing your PC hardware clock with an NTP server so the time is exactly correct...then reboot.

2) Mist starts after syncing, but is a blank white screen. Chances are you are running the "xorg" video drivers on a Linux-based OS (Ubuntu, Linux Mint, etc). Try installing the manufacturer's video driver instead, here is a guide for Ubuntu-based OSes.

3) "Wrong password" notice. This seems to be a false notice on ocassion, related possibly to syncing with peer nodes or something. I have encountered this one myself once. I restarted Mist and the problem went away.