Part of my backup strategy is off-site storage.
So let's assume I have a scheduled backup.  It backs up to a USB external drive. 
Now, I want to protect against theft and fire, so I use a PAIR of external drives.  I alternate them monthly - keeping one off-site.
HERE'S WHERE I NEED HELP:
My backup "job" is set up to save to drive G (for example).  It works fine with the first USB drive.  However, when I swap it out for the Second USB drive, I have no guarantee that the second drive will appear as G.  If it doesn't, the backup fails.
------------------------------------------------------
Now, I have been lying a bit.  The above was an introduction to my topic.  I have played with this issue a bit, but I am dissatisfied.
In truth, I use the Assign Drive letter (Windows XP) and assign the drive letter S.  I use a high letter so I am not effected by Flash Drives, etc. messing up the E, F, G, H (low drive letters) order.
Now, I can't have both external drives in there and assign them both to S.  So I put the first external drive in there, and Assign it S (my backup job, of course writes to S).  I then REMOVE the first drive, and put the second drive in.  I also assign it S.
As far as I can tell, it doesn't work.
--------------------------------------
Now, I've introduced this topic as a seeking of "strategies."  I've done that because I may be approaching this all wrong.
Help greatly appreciated.

Finally, I should point out that I use both Norton Ghost and ShadowProtect from StorageCraft.

Cardinal23, I think the Ghost facility you are looking for is called Offsite Copy which allows you to define two offsite locations (e.g. two USB drives), and then Ghost will backup to whichever one is connected.

Look at the Ghost 14 or Ghost 15 User Manual (see FAQ section) for more info.