It does not work in Skirmish or after restarting a mission. The Rules.ini file is altered and saved.
One thing I did to check if the Rules file was having an effect was by deleting it completely (after making a backup) from the Tiberium Sun directory. I then restarted the game and started a new Skirmish mission, and the game went without a hitch. I'm not sure if this is relevant, but I tried it for the hell of it.
Also, for some reason, TiBed cannot start the game. It isn't a permissions issue; TiBed is using the Game.exe file perfectly well, but that executable does not work when TiBed uses it or if it is used manually. The error is "Failed to initialize. Please reinstall." When I use the shortcut, however, which is routed to the same executable, the game works fine.