I agree with Chani: Look at using Barcelona and Madrid as your gateways. Airfares are highly origin- and destination-specific, so my experience may be very different from yours, but on my two trips to Spain, I found fares to those two cities far, far cheaper than those to places like Seville or Malaga. To avoid an unwanted last-night stay in Madrid, you could fly to Madrid and take a train to your first destination, returning home from Barcelona. Toledo would be ideal for your first night, because it's a short trip and the train tickets do not increase in price when you buy them on the day of travel. So you could spend a couple of nights in Toledo (to have one full day there), then go on to Seville. Seville to Barcelona could be done by air or by train; that's a train ticket you'd want to buy in advance in order to save considerable money.
Incidentally, trying to spend the last night in Toledo before a transatlantic flight home from Madrid is iffy, because transportation from Toledo may not start running early enough for safety. Having to be at the airport 3 hours before flight time makes that plan somewhat risky. I believe it's worse on weekends, but who knows what the train schedules will be like post-pandemic.
Landing in Madrid and spending your first night in Seville (or Cordoba, which is totally worth 2 nights) could work if you decide you don't have time for Toledo, but buying those train tickets after you arrive in Spain will probably be costly (Cordoba being less so than Seville). Buying them ahead of time to save money would force you to guess about a suitable departure time; the inexpensive advance-purchase rail tickets become worthless if you miss the train.
I also agree about not day-tripping to Granada from Seville. I found lots to enjoy in Granada, not just the (magnificent) Alhambra. But then again, I wouldn't travel to Europe in December because of the short days, so I may not be thinking about this the same way you would! There are flight options from Granada to Barcelona; there's also a direct morning express train that takes just over 6 hours.
There's so much to see in Spain; I wouldn't want to add the extra complication (and travel time) of squeezing Lisbon into this itinerary.