A fighter in the Borderlands universe would be interesting. I could see 2K throwing out the guns (for the most part) and making this game based more on bouts like bar fights. Brick and Hammerlock would approve the use of fisticuffs over firepower.
Of course, abilities like siren powers, swords, and Deathtrap would be taken into consideration when it comes to combos. And you know what? Maybe a few hidden guns; this is Pandora after all.