Janie- Welcome to the board. In answer to your question, I can't see any advantage or disadvantage to reversing your route. I did a similar route in 1992, starting in Madrid, and going south through Jaén to Granada, then returning back north through Toledo and into Segovia and points further north.
Your time of year should make it very easy to get around in each of those cities. Will you be renting a car? We did (even for Madrid) and had absolutely no problems (except for a sappy tree that caked our trunk lock shut in Granada...(Avis just swapped cars with us in the next town). I've done it twice since '92 and had no problems with the rentals then either. I believe I've used Avis all three times, renting in the states and then picking up over there. I hope you can drive a stick.
If this is your first trip to Spain, which it sounds like by your do-everything itinerary, I think you've chosen a nice group of places to visit. Segovia should be cool and comfortable in early October, and the crowds will have dispersed, leaving you to stroll the Alhambra and the labyrinthine streets of Toledo in (relative) seclusion.
Enjoy your trip, and as we always say, please post your post-trip impressions!!!