If they'd do a fifth season, I'd want the emphasis back on solving mysteries that the audience has a chance at solving as well. I enjoyed that about the first two seasons.
If they wanted a unifying thread through a fifth season, though... it might be fun to make it around Irene Adler, and maybe kill Sherlock's brother. That could force some interesting character growth. Though Sherlock might be one character people genuinely want to see remain static, so character growth could backfire in a big way pretty easily.
It's really just a shame they killed Moriarty in season 1. He's great, but I don't think they can stretch him out as a bogeyman from beyond the grave any longer.
Edit: oops. Didn't mean to hit angry face.