Donna has stated it well. First thing is a must; you must book with an agent, preferably a cruise specialist and one who has been there. They can not only provide you the best deals, but provide first-hand information that can be invaluable. Plus, their prices will be the same as any online site or the cruise line, so it makes sense to use their expertise when it's free of charge.
As for what would work best for you, it really depends on several things; your age, lifestyle, likes, dislikes, any ports you definitely want to visit, any ports you don't want to visit, and obviously, your budget. This is where a good agent will be extremely helpful to you.
As for when, keep in mind that several cruise lines begin to relocate their ships into the area in April, so after that time you'll have more options available to you.
There are many different ports from which to sail including, but not limited to, Civitavecchia (Rome), Venice, Bari, & Messina, just to mention a few.
There are some awesome places to visit, especially Santorini, which is our all-time favorite place in the area. It is amazing and definitely someplace not to miss. But each place has their own history and beauty, making it tough to decide which ones to visit and which ones to miss. Olympia is very steep in history, as is Athens, and Rome. Venice is a wonderful city - been there 3 times and it's still exciting for us.
The toughest part of a Greek Island/Italy cruise is trying to decide which one is best for you as they are all wonderful.
No matter what you decide, I know you will thoroughly love ever minute of it. We can't wait to go back again and again.