Please stay with colonization! The game mechanics will work much better and make the game far more interesting. You'll be able to get a fanbase. As far as the mod, I'd like to help, unfortunately I doubt there's really all that much I could do. However, I can give you some ideas.
St. Louis as a home port is a good idea, just make a fairly arbitrary city surrounded by Europe tiles, "Europe" of course being the United States. As far as getting to the home city, Wagon trains and railroads have already been brought up, and are good ideas (it would especially assist the western feel if bandits on the way home were a threat). You could also have navigable rivers ala the Chinese Unification warlords scenario and use river barges. I know that to have rivers all the way out west doesn't work for everything, but rivers would be a help if players build cities along the rivers, then wagon-train supplies to the riverain cities and send them back to the home port that way.
As for your forth civ, I would recommend Cascadia or the Republic of the Pacific, both the same state, just different names. The names refer to an idea of a republic formed from northern california, oregon, washington, and british columbia. Yes, I'll admit it's somewhat fanciful, but this whole mod will wind up being that way. The idea is atleast well grounded, and meshes well with your other states As far as leaders, there's always George Abernathy, first governor of oregon's provisional government, John Mcloughlin, head of a prominent fur company at fort vancouver who advocated for an independent state, and the co-founders of portland, Asa Lovejoy and Francis Pettygrove.
Personally for the above leader choice I would like to see George Abernathy and Asa Lovejoy(Lovejoy was more politically prominent than Abernathy, despite losing a coin toss to name portland)
Here's a flag too.
http://republic-of-cascadia.tripod.com/sitebuildercontent/sitebuilderpictures/doug_flag_flat3.jpg
I have a bunch of western music you could use, however, I'm not sure about whether or not it would be okay to use it. the fellows at the ancient mediterranean mod have used images and music from some recent movies, and there's plenty of other similar cases, so if it's not a problem I could email you some music!
As far as the mexico situation, I think it would best as a tribe. That way they'd allow a the first city to be founded (like the texas settlers), but more land would anger them, you'd have to pay, and eventually fight them. Sending your units to mexican cities to Learn professions also works. The only problem I can see with making them a tribe is establishing missions and getting presents form the chief (i.e treasure). I don't know, perhaps they'd also work as a fifth civ that's just on the map.
In the future, perhaps the Canadian west could be included?
I'll also see about getting together some citylists and founding fathers for you.
I'll help however I can, I'd love to see this, and I think it has great potential, as a Nevadan I endorse this mod!