I do a lot of work with multiple spreadsheets, many of them open at the same time. It has always annoyed me that when you double-click a spreadsheet it opens in the same Excel window.
In the past I found that the work around was to open one spreadsheet. Then open Excel from the Start Menu and open the second spreadsheet from within the second instance of Excel. Another workaround on the web talked about disabling OLE in some way, but that one killed functionality I needed.
However today I found a better solution for me. I created a shortcut in the Send To menu that directs files to Excel. When I use this is opens in a second Excel instance.
Details on the Send To: http://www.howtogeek.com/howto/windows-vista/customize-the-windows-vista-send-to-menu/
Still not quite as good as just double-clicking, but much better than a manual open of Excel.