@Redfern
The challenge with all of these ideas is the concern of turning it into another Paul's, Joe's Variety, or even the drab CVS. With the proximity to Preble Street, you'd want to be wary of what you choose to put in there.
A Rosemont-esque location could be ideal for a lot of in-town residents and people working during the day that want to grab a sandwich or some other needed item.
But these are just quick and non-experiential transactions.
Or - do you want to make it a place to go, hang out, a destination? Kind of like an EVO, Wine Bar, Grace (which I miss), Sushi or Thai infusion, Local 188, etc etc?
This way the location is open a little later, lit-up, and safe.
With Merrill Auditorium nearby - and - Portland House of Music just across the street ... it can be a place people go for pre-event tapas, drinks, and so on. It's always nice after a show to get a drink/dessert somewhere too (like in Boston, NYC).