What is the best way to set up multiple iPod / iPhones on the same computer?
You can do the Apple ID any way you like. If you use the same ID on both devices, then you can sync all the Purchased apps to both devices.

I'm using my iTunes to manage and backup the iPhone of my girlfriend and my iPhone. We have separate ID's and iTunes never got confused.

Update

Oh and remember, if you setup up separate ID's then you still can sync all apps from both accounts, but you can't update the apps from your Wife's account on your iPhone, because your phone is set to your account.

This can be avoided by updating all apps through iTunes, though.