I'm no expert, but since indie stores can't seem to beat the big boys in price terms I think their best bet might be to aim for novelty. While I was contemplating this article (ah, holidays) I tried coming up with examples of stores that don't need to exist but do, and do so successfully. My mind went immediately to those rather hip little stores and boutiques that sell unique products made by local or other independent artists.
So here's where I'm going with this: as we all know the casual gaming market is growing like a rash on a fat man (huh?) and traditional game stores such as our much, and legitimately, maligned Gamestop aren't the most pleasant places on earth. In fact, I'd rank them about par with the DMV. Thus, independent game store owners? For the love of god, don't model your stores on Gamestop. Consult an interior decorating book. They have them at the library. That would be rule number one, to lure in new consumers with an attractive environment.
Next, on my brainstorming session of inexperience: the novelty. Boutiques frequently carry products by local artists. For those of you who have never been on Etsy, there's a lively community producing game based arts and crafts ranging from kitschy to outright masterpieces. Contact these artists, ask to help sell their product. Prices on Etsy tend to be low, the crafters will frequently discount bulk purchases, etc. So now you're not just relying on mega expensive games to stay in the black, but also on perhaps more affordable products that both casual and hardcore gamers would lust after.
I guess my main point is that it seems the best way to do this thang, like any other thang, is to look closely at what other types of stores are doing and then adapt their methods to your own end. I know I kept mentioning clothing boutiques, and that's because the parallels between the two stores are so obvious. I mean, EB does stand for Electronics Boutique after all. Hell, I'd go into a hipster-ish looking 'Electronics Boutique' much more readily than I would an 'EB'.
I would like to address LordLocke's point of monetary issues though, because it's a good one. The 'typical' gamer (young males) probably won't have the income to support places I've attempted to describe. However, it's here that we come back to the growing casual gaming market. Say mom or girlfriend likes playing on the Wii (stereotyped example, but bear with me); will she feel more comfortable going into a typical Gamestop where she may get ignored or leered at, or an independent specialty store? I know which one I'd prefer.
All that said, I admit to having no experience in ownership of retail shops, only working them (and not game shops either). Feel free to pick my ideas apart one bloody, sinewy piece at time.