As you scout out all the options, I would make sure to check the "multi-city" option, which would be flying from home to Sevilla and then from Santiago to home. You may find that it is not much more expensive than flying in and out of Madrid, Barcelona, etc. I've done that for years now and it makes my life so much easier, especially on the way home. I fly from Santiago on a 9 am flight and am in Barajas ready to catch an early afternoon flight to the US. Otherwise I would have to come in the night before, stay in a hotel, etc etc.
The fast train (AVE) to Sevilla is quick and easy and very pleasant, but it would not be as quick and easy as transferring to another flight in the airport upon arrival. Of course, you may want to visit the city you arrive in, in which case the AVE is the obvious answer. It's only if you add the internal flight on to your international ticket that the flying option makes sense, at least that's been my experience. Buen camino, Laurie