Our family of 4 spent about 10 days visiting Uzbekistan as part of a 3+ week jaunt through some of the Stans last summer. Not sure what all you are looking for but the following is some of what we did. Note - we are independent travelers and did all of this on our own except for hiring a driver for the Pamir Highway in Tajikistan (Dushanbe-Kalikum-Khorog-Karakol Lake-Osh (Krygyzstan).
Flew into Tashkent on a Turkish Air flight from Istanbul. Our return was also on Turkish Air but from Bishkek, Kyrgyzstan.
Spent 3 nights in Tashkent to overcome jet lag and because we had a friend who took us around. Overall, worth a day of your time.
Next flew on Uzbekistan airlines to Urgench (Western part of the country close to Turkmenistan) and took a taxi to Khiva - ancient Silk Road walled city known for its slave trading past. Lots of medrassas, minarets, and city walls to walk. Hired a cab and went to see some of the many ancient crumbling desert citadels/fortresses on one day (not visually impressive, but interesting when one sees where they are located (desert) with nothing else around) and to think of what this was like when ancient caravans would have to travel these roads. Worth 2 days
Took a taxi across the desert (since there were 4 of us) to Bukhara. 6-7 hours across the hot desert with the Amu Darya visible at times (believe this is the River Oxus from history books). 3 nights in Bukhara. Lots of great blue domed and other historical monuments to visit.
Next, took a train to Samarkhand (~2.5-3 hours). 2 nights. Must see place. World famous Registan and also the tombs of the Timurid dynasties in additional to lots of other things to see. Google these to get a sense of what these are about.
We did not have time to visit Shakrisabz (Timur's home town). From Samarkand, we took another long taxi ride (6-7 hours) to the border of Tajikistan. Crossed into Tajikistan and then took a relatively short taxi ride (45 mins) to the capital Dushanbe.
1) Visa - you will need to get an Uzbek visa - no issues using the embassy in DC
2) People were extremely friendly - lots of folks wanting to take our photographs
3) Safety - I found the place to be extremely safe. Wasn't even worried about pick pockets. There is strong police presence in most places (probably a left over of the Soviet system). On long distance rides, there are a number of police checkpoints where your passport will be checked.
4) Money. Black market rate is significantly better than the bank rate - google it. The Uzbeks don't have any notes greater than 100 som. And since 1$ was worth about 3,000 som, changing 2-300$, results in you getting a stack of notes that is about 3-4 inches thick which you need to make arrangements to carry in your backpack.
5) I always use Lonely Planet (if available). There is a new edition out this year - so check it out for all the details.
6) Summers are hot in Uzbekistan - most of the places above are in the desert - we went in July-August because of the kids school schedule. Tajikistan/Krygyzstan/and Almaty were much more comfortable because of the mountain areas. In fact, some of the high places (12,000 - 15,000 feet) were very cold at nights.
Overall, if you are an independent traveler, you won't have any issues doing it on your own. There is enough tourist traffic in Uzbekistan that the tourist related folks speak some English.
Feel free to ask any additional questions that you may have.