Been to Prague. Simply put, be careful and get a map ASAP! Somewhat confusing city to navigate at first and the underground is efficient enough but takes a bit to understand. Remember that most items tend to be spoken differently than they are spelled, so when riding anywhere make sure you look at the station names.
Make sure to grab some money as soon as you can, which you can do at a train station. Won't get the greatest rate but that currency isn't worth much either. Keep a couple thousand with you and know that everything is in whole numbers, no cents.
I of course recommend you see the Charles bridge and surrounding area. Nearby there is this tower on the hill that overlooks the city and surrounding area, definitely worth it! You can hike up to it but it will take you about 45mins and is a bit steep, or you can ride up in a tram. The castle is interesting enough, most interesting would be the church which is inside the castle walls. It's very impressive.
Just know that they are doing a ton of restoration projects at the moment. Charles bridge, the church, etc.
Make sure you watch all your belongings there, it's known to have a problem with that sort of thing. After going there I can understand why, although I never did. However I also never ventured out at night. Mainly because I walked just about everywhere and saw pretty much all, which was rather tiring. Plus I had no idea where to go for night life. I did walk around a bit near my hostel at about 8:30am, and while I was never in an rough areas I never really felt safe. Course at that time the city is still asleep and doesn't come alive until 9am.
If you have someone with you that knows Czech it would be rather helpful for you as not many speak english(or are willing to) and I found pronouncing anything Czech to be difficult. You may find it easier, I dunno.
Let me know if theres anything you want to know about it. I was there for 3 solid days and walked all over. I can say the food and beer there is pretty good! It's meat and potatoes, so if you like that great!, if not have fun!