My girlfriend and I are traveling to Philly for 3 full days and 1 night in mid-September and neither of us have been before. We are staying in Center City and want to know a few must sees, besides the obvious historical sites, that we should check out while we are there. We are both mid-twenties and want a well rounded trip, including night life, sports, art, history, etc.

Check to see if the Phillies are in town when you are there. It is a nice stadium.

I'm not sure how you can be there for 3 full days but only spend 1 night?

You do know that you need a TIMED ticket to visit Independence Hall, right? Try to visit the Visitors Center first thing in the morning, so that you'll have a good choice of timed tickets.
http://www.nps.gov/inde/independence-hall.htm

Philadephia Museum of Art is an excellent art museum. If you're there on a Friday, check out the music programs in the evening:
http://www.philamuseum.org/artafter5/

Barnes Foundation is a must-see, IMO. It will eventually be moved to a new building/location, so it's even more important to visit it as-is right now. Advance tickets is a must, and it is reachable by public transportation.
http://www.barnesfoundation.org/r_main.html

For sports, you should be able to get tickets to a Phillies game.

3 full days we have to tour. 1 night I have free after a conference.

we arrive late thursday night then have friday, saturday, and sunday. i have a conference during the day monday, hence the one night, and leave on Tuesday.

about 80 hours of free time to be more precise

Before you just stroll up to Citizens Bank Park for tickets right before game time, note that tonite will the 46th sell-out of that park -- the Phillies are HOT. Getting tickets here is not as bad as say, Fenway Park, but it's not a gimme.

Night life -- South Street
-- cultural event on Broad Street
Art -- Art Museum, free on Sunday afternoons.
-- Academy of Fine Arts
-- Rodin Museum
-- Masonic Temple
History -- Liberty Museum
-- U-Penn Anthropology Museum
-- Constitution Center
-- Franklin Court
Other -- Zoo
-- River Bike Trail (good weather)

I would recommend touring the Eastern State Penitentiary. They give you audio guides and you wander around listening to Steve Buscemi narrate different parts of the prison's history. They also have oral histories with former inmates. I'm sure it doesn't appeal to everyone, but I found it fascinating and really well presented.

http://www.easternstate.org/

Make a stop at the Reading Terminal Market for lunch. They have pretty much any type of food you would like.

We also enjoy the National Constitution Center.

A trip to Fairmount Park might also be enjoyable.

Fun and different "must see" sight: Mutter Museum at the College of Physicians

Nightlife: Try the bars and live music clubs in Old City and Northern Liberties neighborhoods. Great restaurants in these areas too. Pick up a copy of Philadelphia Weekly or City Paper (both free) to check listings for music, events and art.

Art: Lots of small galleries in Old City you can visit in addition to hitting the giants like the Philadelphia Museum of Art or the Rodin. Murals and sculpture plus guided architectural walks all over the city if you want to see some outdoor art.

Non-obvious Historical Sites: Check out some of the old graveyards in Society Hill as well as other Philadelphia neighborhoods to see tombstones dating back to the 1700/1800s. Take a stroll down Elfreth's Alley and look at the houses.

Obvious Tourist Traps, But Still Worthwhile for a Quick Overview: Lights of Liberty Tour, Philadelphia Duck Boat Tour, Big Red Bus Tour, Trolley Tour, Ghost Tour

Do the Mutter. A museum of medical oddities. It's fun and close to where you are.

Take the bus or walk across the river (go upwards in numbers)to the Drexel and UPenn campuses. Wander up Locust walk for the Penn experience and then over to Sansom St. for lunch. New Deck tavern has good food and is a fun, casual spot. If you are into archaeology and anthropology, then the Penn Museum is a must-see.

Have a cheesesteak at Jim's on South St. Eat a burger at Rouge on Rittenhouse square. I could go on and on.

You could also drive out to King of Prussia and take the tour of Valley Froge Park. There is also a LOT of shopping there at the King of Prussia Mall.

That should say Valley FORGE Park!

Some excellent ideas. Thanks, everyone. bookmarking

As you move about Philadelphia, be alert to the Mural Art program. These are murals openly displayed, frequently on the sides of older buildings, which are visible because they border on a street, parking lot, etc. You can take an organized tour to help explain the art and the artists or you can do it on your own. We think that many of them are very impressive and unique to Philadelphia.

More info is here: http://www.muralarts.org/