I travel to Prague frequently for work (with a theater company), and these are a few of my favorite eateries where I have also taken other visitors. They aren't "traditional Czech" food offerings, but are places both locals and ex-pats go:
Cafe Savoy, across the Vltava RIver from the National Theatre building -- in an historic building (peep the beautiful ceiling! enjoy the view into the baking kitchen and the wine room as you head towards the restrooms!). Good for brunch, or a nightcap/dessert later in evening.
Luka Lu, just a couple blocks away from Cafe Savoy -- fun, funky decor; Mediterranean food (think grilled fish and meats; and some delicious bread and cheese that's served before the meal); reasonable prices; quaffable house wines by the carafe.
Creme de la Creme or Angelato for ice cream and sorbets in seasonal flavors. Long lines sometimes, and for good reason. (And there's an ice cream museum in the lower level of the Creme de la Creme location on Narodni!)
Artic Bakehouse as well as Bakeshop for bread, pastries, and take-away coffee. Bakeshop also has quiche, soup, sandwiches, salads for eat-in or to-go.
In the Vinohrady area, I like lunch or dinner at U Bulinu (air-conditioned! and good daily specials), or Las Adelitas (authentic Mexican food, and mango margaritas).
Also, check out the Prague Haps FB page as well as www.expats.cz for other food suggestions. The foodie scene has really grown over the last 14 years that I've been visiting, and most of that is locally-grown businesses.
