I've been all over but most recently I've personally driven much of the interior of Mexico over the last year. From Monterrey to Saltillo, Monclova, Cuatro Ciénagas, Matehuala, Zacatecas, Aguascalientes, Leon, Queretaro, Guanajuato, San Miguel, Guadalajara, thru Jalisco and Colima to Manzanillo. Would easily drive thru it all again. At every state border, "detenedor", i was waived thru without issue. Never was asked for money. Times have changed. Not saying there aren't issues but there are old couples from Iowa traveling in RV's again. The beauty of Mexico really is vast. In those areas you see all the landscapes offered in the Texas Hill country, Arizona, South and North, California, South and North and more.
I to would recommend the Potosina outside of San Luis to start. San Luis is more desert like with the Potosina being the oasis. If you drive stick to 57 and the cuota's. Don't go through Victoria/Tampico or Laredo.
Manzanillo is beautiful and wonderful if you are looking to relax. I'd recommend it more for couples, families or older people. Las Hadas is where i usually will stay as it works best for us. Most of your time probably will be spent at the resort with the occasional dinner in town. Its a smaller town. It does not have the nightlife that a Cancun or Los Cabos offers.
South of Mexico City is a whole other set of experiences and another post for another time.
Lastly, San Miguel is nice but overrated. There are 25 towns nicer than SMdA. Why travel all that way to go to see and experience something similar to Lake Travis, only with Californians.
The centro historico of Guadalajara is the best part to me. After a day on the hop on/off bus gives you a good idea of what the city has to offer. It doesn't have the natural beauty Monterrey does. It is more spread out like Houston. Every major city has at least one pueblo magico that is the getaway, think Fredericksburg or Gruene to Austin, that people daytrip to. Tlaquepaque is the primary for Guadalajara.