In Italy, for ruins, head south to the Naples area. You can see both Pompeii and Herculanaeum, then with a slight day trip, the Greek-style temples at Paestum (near Salerno). Combined with Rome, these are the Ancient ruins highlights I've seen in Italy. If you like late roman mosaics, you should check out Ravenna, also.
In Greece, make sure you stay in the "Plaka" district when you're in Athens. All the major sights will be within walking distance, and it has all the amenities -- restaurants, bars, shops, etc. -- that you'll need. If you like Medieval stuff, while in Greece, how about the medieval monasteries at Meteora? They are an amazing sight. Check the pic below...
Also (though I had to skip it on my trip), I hear the ruins at Delphi are amazing.
In Spain, you HAVE to hit the town of Segovia, if you're into ruins. There is a giant Roman aqueduct running through the town, castles, cathedrals, medieval towers -- you name it! Very atmospheric city (can be done on a day trip from Madrid, if you like).
As for inter-Europe flights, yes, there are lots of cheap deals. Plot out a rough itinerary (just a skeleton -- doesn't have to be detailed). For the longer transits, see if you can find cheap flights rather than trains, or whatever.
worldwidemike