if you have a deep wallet, Hayden's on Pine is very good for steaks, and lamb, and a great gin martini and wonderful creme brulee. It is pricy, but I think worth it. A new place, Skewers, is Afghani, huge amounts of good meat on skewers, and the best golden lentil soup *ever*.
I also agree with profjmm that Bricco is really good too.
I moved out of the area about the time of the downtown renaissance so I don't know much about the new joints. I loved the historic Warwick Hotel on Main Street in Hummelstown. I went back on a recent visit but only had a salad. It's a short drive from Harrisburg and the food is great American. It looks like they have a website under construction: thewarwickhotel.com.
About 10 years ago, the only good restaurants in Harrisburg were steakhouses. Since then, several very good places have opened, none of them steakhouses, but all of them downtown. Bricco, Mangia Qui and Bella Mundo are the best restaurants in Harrisburg. I don't know where you're coming from, but they are all, in my opinion, pretty casual. There is also a tapas restaurant above Mangia Qui (same ownership and kitchen) called Suba which has a great atmosphere. Red Door, on Second Street, is a wine bar with good food.