With the new high-speed AVE train, getting to Cuenca from Madrid Atocha station, along with the round trip by the end of the day, has become pretty easy! Although, you cannot go through the sites intricately, and you would have to miss out on many of them too.
The station in Cuenca is 4 km from the downtown. There is the urban bus line number 12 which gets you from the AVE station (Fernando Zobel station) to the bus station, within 15 minutes. There is a bus which leaves at every 1 hour and you can opt for bus no. 1 from there, to get to the upper town for Plaza Mayor. Here you get to see the Cathedral and enjoy the glimpse of city life. Try to avoid your trip on a Monday since all the museums stay closed.
After you have seen the Cathedral, you must get to the hanging houses, which is the main symbol of attraction in the city. These date back to the middle ages and are perched on a side of a steep ravine. They look like they are a part of a cliff. There is one house which holds an excellent art museum inside and is considered to be one of the most important attractions in Spain. If you decide to visit the area, make sure that you get to the balconies for the spectacular view of the gorge.
Make sure that you take some time to cross San Pedro Bridge. It lies at the entrance of the city, and from here, you can get the size of gorges all around the area. If history interests you, get to the archaeological museum and Museo Diocesano for witnessing amazing remains. Visit the churches of San Pedro and San Miguel and take some time out for the lovely gastronomy.