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I wouldn't recommend a car. Driving in Ecuador is an adventure you might want to miss.

Both Quito and Cuenca have comprehensive urban bus transit, you can get anywhere you need to go in the city. Figuring it out is the challenge, but not so hard. Taxis are also abundant and cheap.

I would recommend flying from Quito to Cuenca rather than cover that distance by road. Domestic flights are pretty cheap and it takes only an hour. TAME has tons of inter city flights in Ecuador and the charge is generally $80-100. They also have a nice shiny fleet of new Airbus airplanes. Good service, reasonably priced, on time.

My two cents.

Thank you for your two cents, I agree, driving in any foreign country can be nerve racking.  On top of that know we are all use to our GPS, and I doubt rental cars have those.  Besides we can enjoy the views.  I was checking more so I was armed with facts as to why we shouldn't rent a car!! Hahah

Victoria
You will be better off going by plane, or hiring someone here to go to Cuenca, car rental is quite expensive here, if you want more information just write me.

Marthy

Private drivers run about 100 for the day.  From the airport most taxis charge about 30.  Only use taxis with a red or green boxed number on the side AND the windshield.  Make sure the cameras aren't tampered with or the signs BEFORE you load your luggage OR call a private driver.

We arrived in Quito at midnight two weeks ago from North Carolina.  Arrange your taxi after you clear customs in the Quito air port.  Give them your destination and they will give you a slip with your destination and the cost of the trip so you cannot be ripped off by the driver.  At midnight, our driver drove to our hotel in Quito as though he were in a grand prix.  What a thrill to start our visit to EC! 

During our week in Quito we had to negotiate our taxi fares because none of the drivers used their meters.  So far, in Cuenca every driver has used the meter so there have been no hassels here.

After Quito, we departed for Cuenca.  We debated whether to fly or drive - I did not consider driving here but I was interested in taking the bus to see the country-side.  However, I figured that if the bus drivers are anything like the taxi drivers my wife would be uncomfortable for 8-10 hours with the curvey roads through the mountains so we flew LAN for about $115 per person one way (about 50 minutes). Cloudy day so we did not see much of the country side.

On arrival in Cuenca, we booked a small but nice one bedroom apartment in city center for our two and a half months here.  From Cuenca we will do side trips until we leave in late Feb to go back to NC.

Before I forget.  I was advised not to bring $100 bills because you had to go to a bank to cash them.  I brought them anyway because there are banks all over the place.  In Quito, however, the banks will not break a $100 bill; they will tell you to go to the "Central Bank" which was too far away for me to go.  In Cuenca, I have not had this problem - so far any bank I have gone to has cashed these bills. 

Hope that some of this is helpful from a "newby" standpoint. 

Where do you hale from in SC?  We are very close to Myrtle Beach.