Start with Prague and on to Italy!!

Venice would be nice. Wizz Air and Volotea both fly to it (TSF and VCE respectively)

Smart Wings flies from PRG to CTA in Sicily.

The Naples area can be reached also with Wizz air.

We did the reverse - spending time in southern Italy, then flying out of Bari to Prague via Wizz Air.

A great trick I learned on this Forum: to get a list of where you can fly to from a specific airport, look at that airport's Wikipedia page. (Of course, you then have to confirm directly on the airline's website; remember that not all flights are daily). Here is the list of destinations from Prague: https://en.wikipedia.org/wiki/V%C3%A1clav_Havel_Airport_Prague#Airlines_and_destinations

Looking quickly, I see Italian destinations include Rome Fiumicino, Milan Linate, Milan Malpensa, Bologna, Venice, Catania, Bergamo, Cagliari, Naples, Rimini, and Treviso.

Remember that just because you fly into an airport, you need not see the namesake city. For instance, if you fly into Venice, you can see Padova, Verona, Vicenza, Lake Garda, etc, and not go to Venice itself at all.

Happy deciding!

OK, here is what we did. We drove from Prague.

Went to Cesky Krumlov then down to Vienna, over to Salzberg and down through the Dolomites to Venice. You don't want Venice so you could go to Trieste and then to Croatia, or Padua or Verona, then to Bologna or over to Milan and/or the Lakes. We took 3 days to do travel to those places and we stayed a couple of nights in each, so it is easy to do in your 6-8 time frame.