Itinerary - 6 Nights in Italy

Florence is too important to miss. If it's all the time you have, your itinerary will have to do.
Have a great time.

It's really too rushed. You won't have enough time to do most of the things on your list. You haven't taken jet lag into account nor the time to get between sites. I can't imagine trying to visit the Vatican museums and St. Peter's then going to another museums (you don't mention which of the National museums of Rome you'll visit). It would be too much especially the day after an overnight flight.

Are you flying into Rome and out of Venice? If not, your itinerary won't work at all. If yes, that's much better. I would cut out a city since you really don't have enough time.

Donna

Whew, I'm tired just reading it.
Day 1 - arrive after a long-haul red-eye flight, jetlagged and sleep-deprived. That's not the best condition for seeing major sights. You are likely to spend an hour getting through FCO, then up to an hour getting to Termini by train, then to your hotel to drop your bags. By then, you'll probably want to have at least a light snack and a picker-upper drink before setting out for the sights.
Day 2 - Up early? How'd you sleep last night (some crash, others are up half the night because of jetlag). Which of the Roman National Museums? My fave is Palazzo Massimo alle Terme (near Termini), but since you mention the Pantheon, you're probably planning on Palazzo Altemps. In my opinion, the Vatican has better collections, but you may be interested is certain works. In any case, the Vatican Museums, St. Peter's and another museum is a lot in one day. If you like Caravaggio, stop in the nearby San Luigi dei Francesi church (there's a Bernini sculpture in the piazza) which is lovely in the French style and has several of Caravaggio's paintings.
Day 3 - I guess you and your companion are very early risers. Hope the jetlag's worn off and you got to sleep early on Day 2.
Day 4 - my only advice is to make sure you arrive in Venice with enough daylight to find your hotel. Get exact directions from the hotel. It can be tricky.
Day 5 - Venice is the place to get up as early as possible. It's magical in the early morning mist. I don't know when you're planning to travel, but watching sunrise over the lagoon from St. Mark's Square is a real treat. Most of us think a gondola ride is overpriced. You might consider a gondola rowing lesson instead, similar experience, more fun and cheaper. The best deal is riding in the front of the vaporetto up and down the Grand Canal, early morning and after dark. If the boat doesn't have front seats (some don't), the next best place is the rear outdoor seating.

General comments:

1. If you don't have plane tickets yet, arriving in Venice and leaving from Rome is almost always a better plan. Most flights out of Venice leave early and getting to the airport can take a really long time or can be very expensive. Getting to FCO is relatively fast and easy even for an early flight. Also, Venice is the best place to get over jetlag. It's much quieter, slower-paced and without 'major' sights. You can relax, wander, have a cappucino or a gelato and absorb the atmosphere.
2. Going to Siena from Rome is more time-consuming than to Florence. Same goes for moving on to Venice. Siena's train station is a bit far from the town center and AFAIK it isn't served by the high speed trains. If you want to skip the great art works of Florence, consider visiting a town that has good rail service. Bologna, Padua and Verona come to mind. But with only 6 days, if Florence isn't a high priority, then just visit Rome and Venice. You could easily take a day trip from either to another town. Orvieto from Rome, or even just a visit to Ostia Antica to add variety. Either Padua or Verona could be a day trip from Venice.
   

If you and your companion don't need a lot of time to orient yourselves in a new city, and don't mind just scratching the surface, go ahead. I was younger when I traveled that fast, but it gave me incentive to return. Six days is better than no days.

We just got back from a trip similar to your itenerary, our 1st trip to Italy. Arrived in Rome on a Thurs afternoon. 3 nights in Rome, one night in Trento, one night in Venice, two nights in Florence then back to Rome for the last night. We managed to see everything on your list however....exhausting! I personally would cut out Venice and do Florence. There is so much to see in Rome and Florence. Take all the advice you can from this forum. The replies I received to my questions were extremely helpful, have fun!

I'm sorry, but just reading this list makes me not just tired, but stressed. Every 2 nights in one spot is 1 full sightseeing day. Travel days provide at best a half sight seeing day. By all means choose 2 of your three cities for a six day trip. But Sienna is a daytrip from Florence, not Rome, and stopping there on the way to Venice from Rome would not be time effective. Rome and Florence are much closer together than Florence and Venice. I'd do just Florence and Rome, you will see more.

Flying into Venice and out of Rome is much better, as someone pointed out. Venice would be a much gentler place to start, plus the part about getting to/from the airport and early flight times. What you are proposing on your first jetlagged day is excessive, I never plan any major sights on the first day. I agree with the person who said don't plan additional museums on the day you do the Vatican Museums. On the plus side, days fours and five look pretty reasonable.