I agree that you should, under no circumstance, miss the Alhambra, and that you need two nights (one full day) in Granada to do that.

ssander

I agree with Pal that it's along train ride from Barcelona to Italy, unless you break it up.

as Spain and Italy are your focus, flying to Italy would seem to make more sense.

There used to be a night train from the French-Spanish border to Nice-which could have been ideal for going by train between the two of them but it was scrubbed a few years ago.

Flying or that long boat ride for a divergence and something unique are the only feasible ways to go between Spain and Italy.

If you are going in April, then you have the potential to be in Sevilla for Semana Santa. Even if you aren't Catholic or even Christian. I think you'd find the pageantry of the various processions, floats and religious symbols to be highly fascinating and culturally significant. And if you are, then it will be truly memorable. I did Cordoba as a day trip from Sevilla and for my tastes, that was fine. I agree with kja that Granada merits 2 or better yet 3 nights. But it is so worth it, as the Alhambra is one of the most stunning sights I have seen in the world. Fully agree with a week + for Madrid, with day trips to Segovia and Toledo. I was fine with 5 days in Barcelona, which included a day trip to Montserrat. If you're not hung up on basing in just 4 cities for 7 days each, I'd strongly advise devoting 3 nights to Granada.

I second the idea to be in Andalucía for at least a couple of days during Semana Santa/Holy week April 9-16. The greatest celebration of the year in Andalucía, fiesta and devotion hand in hand, People out on the streets and in restaurants and bars almost 24/7 for a whole week. Could be an experience never to forget.

The Semana Santa celebrations in Sevilla is of course world famous, but the celebrations in Málaga is equally spectacular and less tourists. To give you an idea of the atmosphere, here Diana Navarro sings a traditional saeta from a balcony in Málaga's main street accompanied by one of Málaga greatest sons, Antonio Banderas: https://www.youtube.com/watch?v=u0HHdxt5_kY

About Semana Santa in Andalucía, every little village in full celebration. http://www.andalucia.com/festival/easter/home.htm