Choices:
1) Take the high speed train to Madrid, also visit nearby Toledo and Segovia, then head west visit Avila, Salamanca and enter Portugal visiting the Douro River Valley (Pinhao, Regua and Porto). Then north to see Santiago de Compostela and Galacia before heading east to the Basque region of Spain. Then head north into France through the mountains into Bordeaux region, then north to Loire Valley, then either to Paris (or do Normandy then Paris). From Paris head to Strasbourg, France and the Alsace region. From there you could visit Switzerland or move down to the Rhone River Valley and visit Provence all the way to the French Riveria. Then back to Barcelona.
2) Take the high speed train to Paris, then visit Belgium, Netherlands and Luxembourg (don't miss Brugges and Amsterdam). Then either visit Strasbourg and the Alsace region as well as the Rhone River Valley and Riveria. Then back down to Barcelona.
When in large cities like Madrid or Paris, don't have a rental car, but when you need to travel again pick up another car.