There are a few issues with workspace layout when using multiple monitors, but I'm reporting these as a single bug since I feel they're all related.

1. With multiple monitors, it's hard to tell where one workspace ends and another beings.  My choice of a dark background further confuses the matter, especially with different backgrounds on each monitor.
2. Workspace shape needs to be taken into account when tiling workspaces.
   (see also:  http://bugzilla.gnome.org/show_bug.cgi?id=581833)

These can be seen clearly in this screenshot:
http://picasaweb.google.com/lh/photo/tBAAa-CL1HcLWbl0qdTkkA?authkey=Gv1sRgCJDK77aPmuTOpwE&feat=directlink

What I would suggest is to:

1. Have a border around all workspaces, to guarantee a contrast between the edges of each workspace and the overlay mode background.

2. Use a better tiling algorithm that takes into account the shape of the workspace.  In my case, I think the best layout for my 4 wide workspaces would be to have them stacked vertically (on a single screen).  However, there are many possible monitor layouts (1 monitor, 2 horizontal, 3 horizontal, a 2x2 square, a 3x2 rectangle, even 3 vertical).  

Fortunately, all the basic layouts are all just rectangles with different ratios, so an algorithm capable of neatly stacking rectangles would work fine for the vast majority of situations.

I have no idea how you'd cope with things like T or L shaped layouts (which are theoretically possible), but I doubt you'd come across many people using those.