There's a restaurant just south of Florence, MS called Jerry's Catfish House. It's in the shape of an igloo.
the meteor crater in Arizona has Subwaydome 2061*, which is a Subway restaurant inside a Buckminster Fuller style geodesic dome.
* or any other number greater than 2006, depending on the current mood of Dan and me. We stumbled across it in 2006.
New England Pest Control's giant blue bug along I-95 in Providence, RI.
There's a website devoted to this sort of thing: http://www.roadsideamerica.com/ (http://www.roadsideamerica.com/). It's really about odd tourist attractions in general, but there's a lot of odd looking buildings and structures documented.
I've also seen a PBS special devoted to this too.
I can think of two right in Bedford, PA: Dunkle's Gulf (http://www.ronsaari.com/stockImages/lincolnHighway/GulfGasStation.jpg), possibly the only Art-Deco Gulf station left standing, and The Coffee Pot (http://maps.google.com/maps?f=q&source=s_q&hl=en&geocode=&q=Bedford,+PA&sll=37.0625,-95.677068&sspn=33.160552,79.013672&ie=UTF8&hq=&hnear=Bedford,+Pennsylvania&ll=40.02317,-78.517249&spn=0.003911,0.009645&z=17&layer=c&cbll=40.02313,-78.51716&panoid=SDefw33jSVk3vtj58YY1gg&cbp=12,198.97,,0,0.8), which the organization (http://www.lhhc.org/) I'm involved with helped restore.