How long are you there for, and how much running about do you want to do?
Will you hire a car or use trains?
Will you want to experience a city, or just visit the highlights. We go for the former, wandering the streets to see the nooks and crannies (although walking the Berlin Wall took longer than we expected).
Cadiz isn't massive, neither is Jerez but there is more there.
We've tended to base ourselves in Jerez, Malaga, or Seville for a week or so and do day trips to surrounding highlights. Barcelona will take almost a week to see properly and has a great underground network so you can stay on the periphery a bit cheaper. Seville is also large enough to spend several day meandering around.
Hotels/air B&B with Parking are easy in Malaga and Jerez, but for us driving/parking in Barcelona or Seville was really a non starter and not really necessary.
For Northern Spain (Rioja, Basque region, even across to Barcelona) we take the ferry to Santander/Bilbao and drive across - ferry is not cheap so we've also done a channel crossing and driven down through France and got the long ferry back. Bilbao is also not a bad place to spend a couple of nights but beware hotels with underground car parks designed for Morris Minors.
Airport wise, anywhere that doesn't start from Stanstead works for us. Malaga and Seville airports are easy to get in and out of, as is Jerez but then you limited to your departure airport. The drive from Malage to Jerez is lovely, and you can spend a few hours in Ronda or even stay over a night on the way. Arcos is also en route and there was a great Sunday market last time we were there.
Look for local Festival/Fiesta periods, eg March time Jerez has a Flamenco Festival so the big names are in the theatres, but the bars are full of ad-hoc performances.
Car hire is probably best given a thread of its own
