I'm getting boring but

Glasgow/Edinburgh
Leeds/MAnchester
Seville/COrdoba (fantastic fun)
Toledo/ Madrid
Nimes/Arles
Brussels/Luxemburg
Amsterdam/Haarlam
Vienna/Prague/BUdapest (perm 2 from 3)
Chablis/Auxerre
Bescancon/Colmar

Paris/Amsterdam

We've done Barcelona/Madrid (flying between them on Spanair which cost about $45 per person, and the flight was about 45 minutes!); Brussels/ Bruges/Amsterdam (using the train which was great, and you can fly round trip from the US in and out of Amsterdam, small countries, everything is close); Prague and Berlin (train in between was fine); London/Dublin (using RyanAir; London/Paris (using Eurostar); London/Bath (drove, my sister lives in London and has a car, it can easily be done by train as well).

If you fly into London, you can fly just about anywhere in Europe on EasyJet or RyanAir for a great price -- I've never paid more then $50 for a seat, and all the flights are open jaw. EasyJet even flies to Istanbul and Morocco!

Oops, also Rome and the Amalfi Coast is a nice combination. Takes about 2 and 1/2 or 3 hours on the train from Rome to Salerno, or you can get off in Naples and take a train that goes to Sorrento. Rome is exciting and fun and the Amalfi Coast is stunningly beautiful. Years ago I combined Venice and Verona. That was great as well, and only about an hour apart by train.

Whatever you decide, as there are many options which are great, try not to eat up too much of your time travelling. Public transportation, while excellent, does have drawbacks such as rolling train strikes, etc.(Italy comes to mind) which may eat up some time. I think I might avoid flying due to the amount of lead time you need to make a flight. That could eat up a lot of time. At least in a train, you are looking at scenery.

Are there any two city combos with Seville which includes another city outside of Spain?

ses -- I just checked the RyanAir website and you can fly from Sevilla to Dublin, London, Pisa or Milan! Check it out!

Easy! Florence-Rome.

Fits your criteria perfectly. I for one, like the idea of sticking in one country. The currency, language basics, customs, etc. becomes second nature so you can focus on having fun.

Sesjazz, there are flights on Vueling between Seville and Rome for as little as 50 euros, depending on the date.

www.vueling.com

Aer Lingus will fly you to Paris with a change of planes in Dublin and allow a stopover in Dublin on the return for about the same as a round-trip fare US to Paris on other airlines.

But how many US cities can you get that flight from?

Madrid- Toldeo

Very unique experiences without losing much time in transit. Toledo is a quiet town with a good amount of sightseeing (also more traditional with siesta, etc. ). Madrid is, in my opinion, one of the most fun cities in the world with plenty to see and experience. The bus ride between the two is short and inexpensive.