WildCard is my go-to spot for unique gifts and great cards. It also happens to be right in the middle of Pittsburgh's design zone, Lawrenceville, so not only is the store cool but it's surrounded by other cool stores.
You're certain to find funny cards, cool t-shirts, beautiful stationery, calendars, prints, jewelry, etc. It really is a one-stop-shop, and tends to feature lots of handmade crafty things (think Etsy-level crafting) with a bit of an edge. I once bought a cross-stitch pattern that said "Welcome, Tiny Overlord" to make for a friend having a baby (funny—and apropos!).