I learned to create TextureSet records and apply them as alternate textures to the meshes in the CK. I also learned out to replace a texture that is associated in the mesh itself with NifSkope. The road signs though, are unlike anything I've seen so far.

As far as I can tell, there are three texture files, each with a bunch of signs in them (i.e. \textures\clutter\signage\roadsigns\roadsignscities01.dds) but I can't figure out how the correct one is applied to the sign.

The static RoadSignRiften01 points to RoadSignRiften01.nif which, in NifSkope, is associated with roadsignscities01.dds... which has all the road signs for all holds. So, how does it know which one and what's the simplest way that I could make a new one?

Yeah, signs are wierd like that. Don't worry about what that, though, because it's really easy.

1. Edit the part of the texture that says "Riften", save it, and use it as a texture set.
2. Duplicate the road sign static that uses the "Riften" texture. Give the new static whatever name you want.
3. Apply the texture set to your sign. Because you used the Riften sign and the edited the texture where it used to say "Riften", your new texture will show up in the same place. If you had edited the Markarth texture but used the Whiterun static, it wouldn't have worked, because all those statics are just ever so slightly different from one another.
4. Done.