For the sake of some valid content...
I've been playing a 3-city region all to myself, using a somewhat unusual method. Each city is solely dedicated to one of R, C, or I, and the ancillary facilities are being placed only where they benefit the city's situation (basic educational facilities only in the Res. city but college/uni will be built in the I city, tourism attractions solely in the Com. city, and polluting or otherwise NIMBY facilities are positioned in the Ind. city.
In the course of this playthrough, I've discovered that people are the problem.
My industrial city has no traffic problems and makes money hand over foot by selling the most basic resources (crude oil, coal, etc).
My commercial city had a few traffic issues until I surrounded the city plot with rails/train stations and added comprehensive mass transport options (buses & streetcars). It also makes money by the truckload on account of the gambling casinos and expo center / pro sports stadium I built.
My residential, however, is in near-constant gridlock in the blocks around the highway connection, due to the majority of the populace commuting to work in other cities in the region. It's still profitable, but there's no specific residential-friendly facility to assist in earning $$$.