However, I've seen proposals of a Mexico City - Guadalajara HSR line, like what was once mentioned here: Mexico eyes high speed rail. And I suspect that a revival of intercity passenger-rail service will likely take the form of corridor trains between nearby major cities, including high-speed ones. It may also depend on how much local and state politicians support such initiatives.High-speed bullet trains whooshing across the Mexican countryside. Electric commuter trains slicing through Mexico City. Gleaming new train stations and state-of-the-art switching systems. It’s all part of an ambitious, multibillion-dollar plan to revive train travel in Mexico, a business that was mostly abandoned in 2001 after decades of mismanagement and long, uncomfortable journeys in aging rail cars.
The proposals I've found are for Mexico City - Querétaro - Irapuato - Guadalajara, a total distance of about 300 mi / 500 km, which is reasonable by HSR standards.
If that ever gets going, then the next lines would likely be to Puebla and other sizable cities near Mexico CIty. Monterrey is another big city, but it's borderline for HSR, being 450 mi / 700 km from Mexico City. And Chihuahua and Mérida, despite their size, are even more distant, as is Guatemala City, Guatemala.