My vote for best restaurant in Pittsburgh is Cure. The only thing that would make it better is if they had cocktails (it's BYOB) but that allows you to put money towards food. Make sure you call well ahead for a reservation; I tried a few days in advance and they were already booked, but Jen was extremely accommodating and found a time to get us in. I saw multiple unfortunate couples try to walk in for a table, with no success.
You should definitely start with the large salumi platter for $26. It's not overly filling but has a lot of variety, so you will still have plenty of room for entrees. The locally-sourced menu changes often, and the attention to detail on the plate is just about perfect. Flavors are complex but well balanced. This chef knows his stuff. The lardo was awesome (I actually asked for more for "dessert" and their house mustards were kick-ass. The actually had pig head on the menu (the whole friggin' head came on the plate, too) but they were already sold out by the time we ordered. Next time hopefully.
From a design perspective, they have an open kitchen, with an overall rustic feel to the dining room. I liked it, as it's not pretentious and you don't get the feeling that they're trying too hard. Service was also spot on, being just attentive enough, and doing a good job of what was on the plate.
I can't wait to go back.