Two weeks in Spain Itinerary

Look closely at departure flights, as Madrid may offer more options than Seville.
Overnight in Ronda rather than day trip.
I would also strongly recommend a 4th night in Barcelona.

Day
01. Arrive Barcelona (4 nts)
02.03.04. Barcelona
05. Early train to Madrid (4 nts)
06. Madrid
07. Day to Toledo
08. Day to Segovia
09. Train to Granada (2 nts)
10. Alhambra
11. Train to Ronda (1 nt)
12. Train to Sevilla (4 nts)
13. Sevilla
14. Day to Cordoba-Mezquita
15. Sevilla
16. Depart Sevilla

OR

Day
01. Arrive Barcelona (4 nts)
02.03.04. Barcelona
05. Fly to Granada (2 nts)
06. Alhambra
07. Train to Ronda (1 nt)
08. Train to Sevilla (4 nts)
09. Sevilla
10. Day to Cordoba-Mezquita
11. Sevilla
12. Early train to Madrid (4 nts)
13. Madrid
14. Day to Toledo
15. Day to Segovia
16. Depart Madrid

I agree with David about Barcelona. Unless you have no interest in the modernista architecture (which would make you fairly unusual tourists, but certainly not unique), I think four nights is a minimum there. As I like to say, ten nights wasn't enough for me, and I only did one day-trip from Barcelona. As you start digging into your guide book, your target list for Barcelona is likely to get rather long, and many of its sights require pre-booking because of long ticket lines, which makes putting together a super-efficient itinerary extra challenging.

I think you're perfectly fine with public transportation. Trains will generally get you there a lot faster than a car. Granada requires some bus time, but still is easily manageable without a car.

Thanks for the feedback.....I think we have decided to save Madrid for another trip. Here is our updated plan: 4 nights in Barcelona, 3 nights in Granada, 2 nights in Ronda, 4 nights in Seville, and 2 nights in Toledo.

Sat 9/22: Land in Barcelona in the AM, 1/2 day in Barcelona - Sleep in Barcelona
Sun 9/23: Barcelona all day - Sleep in Barcelona
Mon 9/24: Day trip to Figueres and maybe Cadaques - Sleep in Barcelona
Tues 9/25: Maybe Daytrip to Montserrat? Otherwise full day In Barcelona - Sleep in Barcelona
Wed 9/26: AM flight from Barcelona to Granada. 1/2 in Granada - Sleep in Granada
Thurs 9/27: Granada all day - Sleep in Granada
Fri 9/28: Granada all day - Sleep in Granada
Sat 9/29: Rent a car in Granada and drive to Ronda. 1/2 day in Ronda - Sleep in Ronda
Sun 9/30: Day trips to Grazalema and Zahara - Sleep in Ronda
Mon 10/1: Drive to Seville. Return car in Seville. Sleep in Seville
Tues 10/2: Seville all day - Sleep in Seville
Weds 10/3: Day trip to Cordoba (via train) - sleep in Seville
Thurs 10/4: Seville all day - sleep in Seville
Fri 10/5: Train from Seville to Toledo, 1/2 day in Toledo - Sleep in Toledo
Sat 10/6: Toledo all day - Sleep in Toledo
Sun 10/7: Early train to Madrid train station. Cab to Airport. Flight at 1 PM

Let me know if this itinerary makes sense. I would love to hear some recommendations on places to sleep and/or eat in any of these places. Thanks

Yes. Looks great. You may find however a choice is necessary with your Barcelona day trips, as 1.5 days in the city itself is really not enough.

There is no early train from Toledo to Madrid on Sunday morning; the first train isn't scheduled to reach Atocha Station until about 10 AM, at which time you need to be standing in line at the airport. I adore Toledo but would not spend Saturday night there.

Alright. Lets try this one more time, but in reverse....

Here is our updated plan: 2 nights in Toledo, 4 nights in Seville, 2 nights in Ronda, 3 nights in Granada, 4 nights in Barcelona.

Sat 9/22: Land in Madrid at 6:40AM, Bus to Atocha. Take the AVE train to Toledo - Sleep in Toledo
Sun 9/23: Toledo all day - Sleep in Toledo
Mon 9/24: In the AM take the AVE train from Toledo to Seville. (If feeling inspired, will drop bags off Atocha and go to the Prado museum for a few hours, then return to Atocha and train to Seville). - Sleep in Seville
Tues 9/25: Seville all day - Sleep in Seville
Wed 9/26: Day trip to Cordoba (via train) - sleep in Seville
Thurs 9/27: Seville all day - sleep in Seville
Fri 9/28: Rent a car at Seville Train Station and drive through Grazalema and Zahara on the way to Ronda. Sleep in Ronda
Sat 9/29: Ronda all day - Sleep in Ronda
Sun 9/30: Drive from Ronda to Granada. Drop car off in Granada (should we drop off at airport or train station???) - Sleep in Granada
Mon 10/1: Granada all day - Sleep in Granada
Tues 10/2: Granada all day - Sleep in Granada
Weds 10/3: Early afternoon flight from Granada to Barcelona - Sleep in Barcelona
Thurs 10/4: Barcelona all day - Sleep in Barcelona
Fri 10/5: Barcelona all day - Sleep in Barcelona (Maybe a day trip to Figueres)
Sat 10/6: Barcelona all day - Sleep in Barcelona
Sun 10/7: Fly home from Barcelona at 1 PM

I feeling like this one may be a winner....

Yes, that avoids the last-night rush back toward the airport, and it makes your first day more productive than it might ordinarily be by getting you to Toledo.

I would feel rushed with the time you've allotted to Toledo (I'm brain-dead on arrival day) and Barcelona, but if you love them as much as I do, you can re-visit them when you return to Spain to catch Madrid, Segovia, etc.

You can save a fair amount of money by purchasing your AVE tickets (and the Granada-Barcelona flight) very early, but that will tie your hands, schedule-wise. I mention this since you said you might want to spend a few hours at the Prado on the day your move from Toledo to Seville. Rail fares from Toledo to Madrid do not vary, so you have flexibility for that part of the trip and should be able to buy the ticket for the first leg on the day of travel. You might opt to pre-book the Madrid-Seville leg for later in the day, then make a decision in the morning as to whether you want to spend some additional time in Toledo or head right to Madrid and see part of the Prado (or do something else).

Just don't miss that train out of Madrid! Atocha station is rather large and potentially confusing. There are often uniformed Renfe employees in the ticket lobby, available to point you in the right direction, but this is not a station where I'd want to have rush for my platform.

Your reverse plan looks good, and it is very similar to the trip that we took last fall. We are wine lovers, so our day trip from Barcelona was to Sant Sadurni d'Anoia for the cava producers and while there we also went to Simon Coll for the chocolates. While in Granada, we stayed at Casa del Aljarife. It is a wonderful little B&B in the heart of the Albaicin and Damian, the owner, is a wealth of information on local restaurants, the Alhambra etc. Great place if you want a real feel for the local scene in Granada. I agree with the previous poster's comments on Atocha. The station is probably the most confusing we've ever encountered in our travels, and the personnel were not very helpful, so do leave plenty of time. Another word of caution is to really pay attention to the speed limits when driving from Granada. There are numerous speed traps and cameras. Speed limits go up and down, and up and down very rapidly. Receiving one of their tickets upon arriving home is very expensive. Not only will the Spanish authorities send you a ticket, but the rental car company will also charge you a ridiculous amount of money for "providing the authorities" with your contact information. The drive through the Grazalema Forest is beautiful. Enjoy your trip!