I know this is a matter of opinion, so let's hear your opinions and, more importantly, what factors went into forming them. Just for the record, I will be there with my daughter, age 15. Thanks, Craig
We stayed for a week in an apartment off Old Town Square. It was a really good location and within walking distance to many of the site.
Most of the areas of interest to tourist all sit within walking (or very quick public transit) distance of each other, so it's hard to nail down what is the one "best". Outside of the communist-era concrete jungle that most tourists avoid, I would probably put the area around Wenceslaus Square a little lower on the list. Although nice enough, there isn't a whole lot here for tourists to see and it sits the furthest away from the Old Town and Castle areas. Between the Old Town, Little Town and Castle... flip a coin, they're all pretty nice, if a little Disney-fied.
I stayed in Holsivice and loved it. The old town and castle area restaurants and everything were overpriced and the food was not good. Everywhere I went in Holsivice was about half the price and excellent. The only problem was oredering as no one spoke English. I was lucky that I was with someone who spoke German because most Czechs understand that.
My daughter (age 22) and I just returned from Prague and we really liked the south side of town because it was away from the busyness of the tourist areas. The metro and/or tram is accessible pretty much everywhere. See my posting under "Hostels" on the Graffiti Wall if you are interested in the hostel option. It is a great way to meet people from all over the world!
I think the ideal location would be about a block away from the old town square. We were farther away and up a long hill which got very tiring at the end of the day.
Craig,
Definitely the Old Town. It's centrally located and has the most atmosphere, cafes, etc. It is wonderful to wander around in the evening and not have to walk far to get back to your hotel! Make sure to take your daughter to the rooftop terrace at the U Prince Hotel, even if just for an appetizer. The views are great and our kids loved looking down on the Old Town Square and watching all the action.