Fortunately, a 12-hour layover itinerary for Mexico City can include the short time it takes to get from the airport into the city-center. It's not that far away!
There's still plenty of time to check some things out, even if your ultimate destination is elsewhere.
You really can get back to the airport - having seen and experienced a lot of Mexico City - even in just a few hours.
One can easily arrive to the Zócalo from the Airport, by taxi, Metrobus, or by Metro to Metro station "Zócalo." The Metrobus Linea 4 (take the South Route/Ruta Sur) from the airport and get off at the station "Museo de la Ciudad." You can't miss the Zócalo. It's just four blocks north.
From the Zócalo, you can't miss the Palacio Nacional. It makes up the entire east side of the Zócalo and it's a good way to get your bearings. Inside, you'll find one of the most famous of Diego Rivera´s murals. Entry is free and you'll need to check your bags.
It seems almost ridiculous to put the cathedral second, as it so dominates the entire Zócalo area. But you can go at your own pace, to one or the other first.
The Metropolitan Cathedral will deeply interest those pursuing colonial and viceregal history, and those with an interest in art and architecture. For the spiritually minded, Catholic or otherwise, it's the center of Catholic life in Mexico.
The Postal Palace is just one of those spectacular public buildings that never ceases to amaze. It's still operating, though, for many of us, snail mail is not quite what it used to be. It's still a wonderful place to peer into and it doesn't take all day. In fact, an hour's visit is quite enough.
Next peer into the second Sanborns restaurant in the world...
At lunchtime, on a weak traveling stomach, Sanborns nearly always has something light and not terribly taxing. This Sanborns just happens to provide even that much more of a feast for the eyes. You can read more about it here. With lunch, a visit should take about 90 minutes.
You almost can't visit Mexico City without taking in at least a little bit of the Alameda. It's most charming, entirely geometrically in the style of a formal garden, and it's the first real city park in the Americas. Here's a bit more about it (plus some photos).
As it houses but one painting, the Diego Rivera Mural Museum is frequently overlooked in Mexico City's enormous quantity of world-class museums. This one houses a mural Sueño de una tarde dominical en la Alameda Central.
From the Alameda, one need only head south through the neighborhood of San Juan Moyotlan (technically it's Centro Histórico, Area 5) to souvenir heaven and shopping!
The Ciudadela Market is a fantastic way to close an afternoon prior to your trip back to the airport.
Everything is listed below, to make it easy. Now get going.