Madrid or Naples?

Personally I would choose Madrid because I haven't been there yet. Prague to Vienna 4 hours by train, to Budapest 7 hours, to both many direct trains a day. To Krakow only one overnight direct train. Few more with change in Katowice. The easiest to get from Prague is Vienna then Budapest, more complicated to Krakow. All three cities are worth seeing. Everybody can rate them differently, my rating: 1. Budapest, 2. Vienna, 3. Krakow. There are many direct trains from Berlin to Prague - about 5 hours.

I haven't been to Madrid yet, but aside from the food in Napoli, you are close to the Amalfi Coast, so the possibility of the big city and the gorgeous coast is something to consider.

Naples has excellent museums too, such as the archeological museum. It's really hard to choose across two different places without knowing what aspects of each appeal to you (and what exactly you want to do there - this is highly individual so I'm not sure how others' preferences really matter). I found Naples really fascinating and a good gateway to other sites I wanted to see. Vienna and Budapest are bigger than Krakow - the historical part of Krakow is quite compact and can be covered in 3 days. Again, it depends what you want to see around each city and in each city. Krakow is the closest jumping point to the Tatra mountains and Aushwitz, whereas Vienna and Budapest will give you access to other attractions. I'd start with a "must see sites" list to try to cull what really speaks to you the loudest.

Although budget flights make it possible to include Madrid or Naples, I would stick to a more traditional, cohesive, somewhat compact route in the north. Vienna has great art museums and palaces, equal to or better than Madrid. Krakow is the longest travel distance from any of these cities, but when are you likely to get any closer? Each country does have enough differences that you won't feel you are repeating.

Thanks to all for the usual great advice. In truth, I would like to just do Berlin, Prague, Krakow or Vienna, Budapest then fly home from Brussels. But I'm trying to appease my better half, who wants to go to Italy again!

I think the places you want to go make sense. If you have to throw in Italy, continue south from Austria and visit the parts you have to. I'd personally stop short of Naples (especially in warmer months) and tour northern Italy.

I'm worried you will visit Madrid and hate Spain. Madrid isn't indicative of Spain at all, it has virtually no history. Barcelona considers itself Catalon, rather than Spain, but it's a great city - if you have to pick only one, pick Barcelona over Madrid. Even then realize there are distinct parts of Spain you can't possibly experience visiting only one place.

IggyStooge, so it's settled, you are going back to Italy (for your better half).