There's nothing wrong with having one of your 3 monitors be the spreadsheet machine. I do this as well, and let me tell you, that spreadsheet is the heart of my business. I have about 20 tabs in it and I can immediately update each part of my business immediately and then return to center screen for work in progress.
If I had to flip around and pop up the spreadsheet to make one tiny change, and then lower it again, then back and forth, I'd go crazy.
You asked about a methodology for monitors, but keep in mind a programmer/developer will have have a diff't need for them as would a PPCer as would another industry vertical, it's really up to you.
For me personally?
Far left (Monitor 1): Static spreadsheets, data scrubber always running in background processing data, Direct TV feed for watching movies.
Central (Monitor 2): Email, Trillian, Browsers, To-Do Lists, etc.
Far right (Monitor 3): Development machine, script work (all source code), etc.
I have all 3 with real-time backups of the data to Carbonite.com, so when I walk away, all newly changed data is backed up automatically.
Does your software handle the ability to say, take a window from monitor #2 and drag it into monitor #1, etc etc? That's important, too.