The AVE service is still being rolled out across the country. The original south-west arm of the service takes you to three very important cities - Seville, Cordoba and Toledo, while the service was also recently extended to Barcelona in the north-east.
Below are some guided tours that take you to Seville and Cordoba or just Seville. Only with the AVE could you cover so much ground and be back in Madrid so quickly! If you'd prefer to organize these excursions yourself, you can book just the train tickets here: Book AVE in Spain Tickets (book direct)
There used to be an AVE tour of Toledo, but this has now been discontinued. But you can still book a similar Toledo Guided Tour, only without the AVE train.
Tour of Seville by AVE
Length of Tour: full day (13 hours)
Take the AVE in the morning to Seville, have a three-hour guided tour of the city and enjoy free time in the city before your return journey in the evening. Only with the AVE train can you get over eight hours in Seville on a day trip from Madrid.
Tour of Cordoba & Seville by AVE
Length of Tour: Two days
This tour adds to the above tour by including an extra city, an extra day and night (including accommodation, dinner and breakfast) for not that much more money. Unfortunately, the only way such a tour is possible, budget-wise, is by using a bus instead of the train for the outbound journey, thus eating into your time drastically. I'd say it is worth the extra 90€ for the extra city and extra time Seville (especially considering you have meals and accommodation included), but all that travel in two days is not for everyone.
Tour departs from Madrid on the morning of day one and features a guided tour of Cordoba before ending your day in Seville. On day two you are taken on a guided tour of Seville before returning to Madrid in the evening.