You really need to think about what you want from your river cruise. Virtually every line will sail to most of the same ports. Like others have said, AMA Waterways, Uniworld, Avalon, Tauck and Viking do cater to North Americans - or basically English speaking passengers. The ships are essentially the same size but the guest to space ratio is better on certain lines. All except Viking will have some active touring components such as biking and hiking options for included excursions. All except Viking will generally give you a choice of 2-3 options for excursions in each port. Food is subjective, but some lines will have better food. As for getting to a larger city - most of these lines will offer pre and post cruise extensions. On the Danube we started out in Prague for 3 nights (amazing city) and then we were taken to Nuremburg to start our cruise and we ended in Budapest and stayed an extra night there as well. The pre and post options really help round out your trip, but be aware that they are a bit expensive for what you really get, but they are convenient.