If you end up going to Mexico, it might be worth spending a day or two in the pleasant colonial city of Queretaro, which is located between Guanajuato and Mexico City. It's another safe town, and has a nice pedestrianized colonial core, even though the surrounding area is booming with lots of foreign investment.
Another thing to consider is flying into BJX airport near Guanajuato, and flying home from Mexico City, or vice versa. BJX is a small airport with direct service to the US. The airport is mainly there to service the nearby industrial city of Leon, but it's only 30 minutes by taxi to the city of Guanajuato. I think that American, Delta, & United all have flights there, mostly on regional jets from their US hubs.
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