Flying from Orlando Florida to Madrid or Barcelona and head south to Andalucía for a 3 to 4 days visit. Come back to Barcelona to take a Mediterranean cruise .
Madrid is 2 1/2 to 3 1/2 hours to Malaga by direct train. From Barcelona it is 5 1/2 to 6 1/2 hours and mostly with a train change in Madrid.
Madrid is significantly closer to Andalusia than is Barcelona.
If you land in Madrid in the morning or even early afternoon, take the train to Cordoba (via Madrid Atocha station). Stay there and day trip to Sevilla. Cordoba is smaller and quieter than Sevilla, so it's a better place to get over jetlag. Then take the train to Barcelona.
If you're going in summer, Andalucia may not be a good choice because of the extreme heat, even in Madrid. Consider flying into Barcelona and spending time in Valencia or Zaragoza.
Just a little note on the heat : Zaragoza is barely cooler than Andalucía in summer ; 100F temps are common. If heat is a concern, then stay on the coast - Valencia is a good call.