Say your protagonists are best friends, or that your protagonist has a best friend. Potato, potata. You could say there's something unique about a best friend relationship, but they're not one-size-fits all even in fiction.
One big factor in a best-friend bond is gender. Would you want these friends to be the same gender, or opposite? If the same, are they M-M or F-F? What different themes could you explore, and what plot devices could you use based on gender? If nothing else, their genders would affect how others percieve their relationship and whether or not it is socially acceptable.
Crime-fighting women? Boys who discover a magical other-world? Or perhaps a boy-girl team who save a mistakenly convicted felon from the electric chair?
And while your best friend team is off saving the world, is there anything that would challenge their relationship? Do they grow apart? Fall in love? Does one decide to fall in with the bad guys?
Feel free to answer/ramble in the comments. If the question inspires a Flash Friday or something similar, feel free to link to your story in the comments and please link back to here on the applicable webpage.
Best friend team GO!