I love Prague. I was lucky enough to spend a weekend there last winter and a day and a half there just last week. There is so much to do in the capital of the Czech Republic, but it's tough to do it all on a short amount of time. I've been lucky enough to skim the surface of the city with just a few days total, but there really is plenty to do. If you have the opportunity, I'd recommend more than a weekend in Prague, and here's why:
There's more to see beyond the walking tour
Don't get me wrong - the main stops along a typical Prague walking tour are amazing: Prague Castle, the Charles Bridge, Old Town Square, etc. It's the side streets that spark my interest though: the little alleys lined with shops, cafes, or just even graffiti that deserve a walking through. Unfortunately with just a weekend, there isn't as much time to get lost.
The nightlife is crazy
If you like to go out at night, there is an endless supply of places to go. Prague is known for nightlife, and with just a weekend you won't have the time to experience it all.
Things are cheap (ex: beer is cheaper than water)
If beer is your drink of choice, then you'll be able to afford plenty with meals or when you go out at night. (One beer at a bar came to about $1.20 USD). This also means you'll have some leftover cash to spend on food, shopping, entertainment, etc. With my day and a half in Prague last week I spent a total of 500 Kc ($25 USD) on food and drinks. Had I had more time, I would've used this opportunity to go shopping and save some cash!