Escazu Chocolates on Glenwood Avenue - totally yummy, and made on site. Get a cup of spicy hot cocoa for yourself while you're there.
Stitch by Holly Aiken on Wilmington Street - uber-hip handbags and accessories for women, also made right there on site.
Great Outdoor Provision Company in Cameron Village (also at Eastgate in Chapel Hill) - parkas, kayaks, tents, fly-fishing equipment, etc.
Actually, there are a lot of small mom and pop boutiques in Cameron Village and North Hills in Raleigh. I really like Beleza (fair traded jewelry and accessories) and Hand Picked (silver and non-precious stone jewelery) in Cameron Village and Haven (really, really, ridiculously pretty home accessories, though expensive) in North Hills.