horseshoe846 - thanks for the reply. I assume you can still use money instead of having a transponder for the cuotas? It's been about 8 years since I drove on a cuota.
The second level that Horeshoe846 mentioned requires the transponder as do some other toll roads in CDMX. The normal toll roads (cuotas) outside of CDMX still take good old pesos. The two toll booths north of CDMX you will encounter en route to Queretaro take either transponder or pesos.
I'm not sure that if you are starting from the airport on a Sunday afternoon you will get a huge improvement from getting up onto the 2nd level of the Periférico, but that is always a crap shoot.
Driving in the centro of Queretaro is surprisingly easy and low stress. It is mostly laid out on a simple grid system with alternating one way streets. I drove around it at night the last 2 nights and it was quite easy to navigate at night just using google maps. Beware that there is some construction going on and several streets are closed. I ran into this the last 2 days but it was pretty intuitive to figure out alternative routs around the work.
San Miguel is a bit more of challenge because the street layout makes a little less sense, but it still isn't bad at all to get around as long as the traffic is not terrible like it sometimes can be.
Guanajuato on the other hand is a nightmare to drive in the centro -- day or night. I lived there and drove around it for 5 years, knew perfectly well where I was going and knew all the tunnel entrances and exits, and it still drove me nuts. Find a place to keep your rental car parked for the duration of your visit and walk or use cabs; the stress reduction will pay for the cost of the cabs.