You would need to edit the theme, to change the widget areas and sizes. The current widget system isn't advanced enough to do that alone. Also, the widgets currently reload every page change, which will look strange if widget content doesn't. But overall, it would work.
I would ditch the widgets and use a theme with that as the main layout. Then if you need to change the side bar, you can use some simple js to change it when a particular page is loading. Of course, this would not work if you are planning to use a lot of the existing widgets.
