I've been rolling around a similar idea for a year or two now, but I was thinking one-on-one: a GM plus a PC. It would be more of a "day in the life of" RP experience, focusing as much on the setting itself as the particular job at hand. I am inclined toward a Street Scum setting, rather than a Prime Runner "Rambo vs. Everyone" experience, but that was more a matter of personal preference about which aspects of life in 2075 I wanted to explore in greater detail. The protagonist in question wouldn't need to be a shadowrunner, necessarily; just a chummer or chummette trying to make their way in the giant, unforgiving world, as Poindexter said.
Chemistry between the player and GM would be critical, even more so than it usually is. It would be as much of a collaboration as it would be a traditional game. In fact, in my ultimate vision there would be two games running parallel to each other, and in the second one the GM and the PC would swap roles. This is mostly because I'd also like to play in this arrangement as well as GM it.