Cant make a decision, LOL. Spain >>> OR >>> Portugal & Spain ?

FYI there is no direct train service Barcelona to Seville. You would change in Madrid. That trip takes at minimum 6 hours.
Why not fly into Seville and out of Barcelona and save Portugal for another trip

So if I am understanding this correctly with 12 days you will start in Barcelona, then head to Sevilla, then Granada, to Toledo, and then Madrid.

Have you thought about adding the fantastic town of Córdoba to your mix? Even as just a day trip from Sevilla? I think no visit to Andalucía is complete without seeing the Mezquita de Córdoba. I would even recommend spending at least one night in Córdoba. Along with one of one of the best attractions in Spain, the Mezquita de Córdoba, it also has many other well-preserved Islamic architecture, as well as pre-Islamic Roman ruins.

If you would like to use public transportation, as Jazz+Travels pointed out, their is no direct train connection between Barcelona and Sevilla, one has to go via Madrid. You could consider restructuring you itinerary in this manner:
Fly into Barcelona
Train to Madrid
Train to Toledo
Train to Córdoba
Bus to Granada
Bus to Sevilla
Fly out of Sevilla

I like the idea of flying home from Seville....yuk when I check the air prices it added almost $3000 to our flights for 4 people. Our fight in Barcelona and out of Madrid are only $2800. Doing the Seville departure brings it to almost $5800. Will do some more searching, I have till 8:30pm to cancel our flight. It also appears there is a train from Barcelona to Granada. Hard to determine times and availability, seems you need to go on 60 day prior to nail this down. We were planning to do a rental car to get from Seville back north in order to have flexibility to make stops between stops. Figure when going from Seville to Granada we can stop in some of the hill towns Rick Steves mentions in his book. Thanks for the Cordoba tip, will try to work that in the itinerary.

Issues like this come up on this forum about once a week, so you're not alone.

While we in the US think of Spain and Portugal as practically one country, they have surprisingly skimpy transit links between them, and are surprisingly difficult to combine in one trip. Spain is also a larger country than it first appears (again, from a US perspective) and driving some of your routes takes time (the high speed trains, where they exist, can be twice as fast as driving).

Between the Spain and Portugal there are trains (very very few, often at odd hours), there are buses (fewer than you expect and requiring more changes than you would think) and there are flights (more than you would think, due to the lack of other options). You can rent a car, but a car picked up in one country and dropped in the other (your original idea) will have a surcharge of several hundred euros.

With only 12 days, you'll find it much easier to pick one country or the other, rather than trying to combine them.

For your second itinerary, it works better as follows: Fly into Barcelona. Flight from Barcelona to Granada. Train (or bus and train if construction on the high speed connection is not finished) from Granada to Seville. Train from Seville to Toledo (changing in Madrid - easy). Train from Toledo to Madrid. Fly home from Madrid. That's still very rushed, and leaves only a few days in each place, but is at least doable.

Personally, with only 12 days, I'd pick two of the three:

Madrid and around (Toledo, Segovia, etc.).
Barcelona and around (Montserrat, Girona, etc.).
Andalucia (Seville, Granada, Cordoba).

You do not have to look 60 days in advance to get idea of the schedule The train routes do not change.

Yes, what Jazz said. You can find out today how long it will take to travel each leg by train, and approximately how often the trains run on each day of the week. Just use next week's dates. If you buy your tickets way in advance once they are available, you will pay substantially less than the fares you see for next week, except that I don't think fares between Toledo and Madrid change. Simply for checking schedules I like to use the Deutsche Bahn website.

There is AVE service along the route Barcelona-Madrid-Cordoba-Seville. A car will be much, much slower than the train along that route. Use ViaMichelin.com to check driving times.

You don't have much time and are thinking about a lot of cities (too many for my taste). You don't have time to take advantage of having a car by wandering around the countryside; you'll need to rush straight from city to city.

If you have a strong desire to take a road trip to Spain, just plan on Andalucía and a bit of time around Madrid/Toledo. You can take in the white villages, where a car is really handy. That means dropping Barcelona from this trip and not having a great deal of time for the Madrid area. I don't recommend this if you like art and want to hit the three major museums in Madrid as well as the glorious Toledo.

Madrid is a large country. It has many great destinations (you're only scratching the surface), so don't try to do everything in one trip. And definitely don't try to travel to both Spain and Portugal in twelve days!

Edited to add: It is sometimes not cost-effective to fly in or out of Seville (or Malaga). I'm flying into Madrid next April myself for a trip that begins in Andalucía, because it was many hundreds of dollars cheaper. But my trip is a long one and I am not pressed for time. I will spend the first night in Madrid, allowing me to buy a super-cheap rail ticket to my first stop (probably Seville) for the next day without worrying about missing the train. On a shorter trip I might make a different decision--but then again, I am not buying four tickets!

Wow, great tips. I actually found that airfare from Barcelona to Seville is about 39 to 59 euros depending on what time of day you travel. And the trip is about 1.5 hours. This would save over a US to Seville flight....and eliminate a stop over. Most of the flights I could find into Seville from the US brought me into a 14 to 18 hour flight with the layovers. A direct flight is 8.5 hours. I have been looking online for several weeks now. Cant make sense of the prices. One day they doubled, next day I found a cheap flight and later in the day they jumped again.

Fare movement is unpredictable beyond the fact that it is highly likely to happen. My best advice is to identify the options you consider acceptable from the schedule standpoint, try to have a bit of flexibility as to dates, and check those fares every.single.day. I keep a record of what I see in an Excel spreadsheet, but a piece of paper will work just fine. Once you determine the typical range of fares, you'll know an unusually a good one when you see it, as well as an unusually bad one. I caught a $300 fare drop a few days ago, and I pounced.

Last year I was flying to Budapest and back from London. I paid close to $900, not a particularly good fare, but I had watched for quite awhile and nothing good seemed to be happening, and there weren't many routings that were attractive to me. I continued watching for some time after I bought the ticket, and I saw that fare bounce between $800+ and $1300+ over and over again. Totally incomprehensible.

One thing to be aware of is that it seems (to me) that while connecting-flight fares may continue to drop occasionally as well as rise until you're within a few months of the departure date (and possibly longer, depending on ticket demand), that may not be the case with non-stop flights and connections that are markedly better than others. In other words, the spread between the expensive tickets and the cheap tickets tends to widen. Travelers have different willingness to accept long(er) layovers to save $100, $200, $300. If you fall in the "heck no" category where long flights are concerned, it's safer to focus on those flight gyrations in the fall rather to still be shopping around in January or February.

Remember, though, that if you book a train or a separate airline ticket to your ultimate destination, the risk of missing that train/flight due to a transatlantic delay is all on you. You do not have any protection (unless you have the appropriate sort of trip insurance). It's completely different if you buy a connecting flight all the way to where you want to be. So if you want to start in Andalucía and are looking for tickets into a cheaper city than Seville, I'd check Madrid first, rather than Barcelona. If you have a disaster and miss your flight (or train) to Seville and have to buy a full-fare replacement ticket, a train ticket from Madrid will probably cost quite a bit less than one from Barcelona, and of course the trip from Madrid will be much faster. With short-hop flights, who knows?