We took a bus from Madrid to Toledo (no problems at all).
When we first arrived in Madrid we reserved (at the airport) our seats for the AVE train to Cordoba. There are plenty of trains, but we want reserved seats in the non-smoking train at a certain time.
The AVE trains are very, very comfortable, and of course very fast. I love trains!
We took the AVE from Cordoba to Sevilla as well. When we arrived in Sevilla I wanted to book the train to Granada, but the line at the RENFE office was very long, and there was only a 16:15 train in the afternoon which didn't suit our needs.
In the end we took the bus from Sevilla to Granada (3 hours) and did not book this in advance. By chance we arrived in the bus station half an hour before the bus left and had no problem getting tickets for the 12:00 bus (the next one was at 15:00).
When we arrived in Granada we reserved our bus trip back to Madrid.
In short, we found both the buses and trains very comfortable - and if you want to work things out on a tight schedule, best to book things out in advance.
Best,
Ellis