StoryPeople has an unbelievable selection of unique and meaningful artwork. It's a great gift - I'd know, having given and been given one in the past...
For a more handmade gift, I recommend Etsy, of course! Here's a few of my favorites.
a beautiful casserole dish from SierraClayArt
jewelry by PoleStar
stationary by Morris&Essex
Or, TomsShoes are always a great gift idea.
And, if all else fails, you could always save the earth on their behalf...
Visit Oceana to adopt an environmentally-threatened creature!
Or visit Renewable Choice for renewable energy and carbon offset gifts!