Python Back-Up Script
You can simplify paths using forward slashes:

GOOGLE_DRIVE_DIRECTORY = 'C:/Users/Jeff/Google Drive/Manifest_Destiny'
MAIN_BACKUP_DIRECTORY = 'C:/Users/Jeff/Desktop/Manifest_Destiny_Backups/md_backup_{0}'
EXTERNAL_DRIVE_DIRECTORY = 'F:/My Files/Manifest_Destiny_Backups/md_backup_{0}'


Instead of converting a date to a string, which may be locale dependent too, and then replacing characters in it, better to use strftime to generate exactly the format that you want:

def get_backup_directory(base_directory):
    date = datetime.datetime.now().strftime('%Y-%m-%d_%H%M')
    return base_directory.format(date)


If a variable contains a format, I would suffix it with _fmt or _format to clarify.

I don't really like global constants inside methods, so I would split copy_files like this:

def copy_files_to(srcdir, dstdir):
    for file in os.listdir(srcdir):
        file_path = os.path.join(srcdir, file)
        if os.path.isfile(file_path):
            shutil.copy(file_path, dstdir)

def copy_files(dstdir):
    copy_files_to(GOOGLE_DRIVE_DIRECTORY, dstdir)


The advantage of this is that copy_files_to is easier to unit test. I think it's also good to use more specific names for the directory variables to clarify which one is a source and destination.