Hey Jeremy,
Not in the Keyboard Maestro Editor.
You can export the macros – do a find/replace in the XML files – and then reimport them.
TextWrangler (or BBEdit) will let you do a multi-file search/replace.
This is not simple, but it's doable.
In general macros accessing the file-system should use relative paths for portability.
So instead of:
/Users/your-user/Downloads/your-file.txt
You'd use:
~/Downloads/your-file.txt
There are Expand Tilde in Path and Abbreviate Tilde in Path filters.
The OSX Go-To pop-up menu understands $HOME-Notation paths (e.g. ~/).
Keyboard Maestro also understands that notation in fields that require a path.
-Chris