This is actually based on a comment I added to an article about replacing Joe Biden as VP on Huffington Post. My own answer is yes, he should step aside, mainly for the reasons below, most of which were not addressed in the article.
This article raised the political considerations and then ignored the most important factor--the neo-GOP nominee. The best V-P pick to balance the Democratic ticket will crucially depend on who President Obama is running against. I actually like Joe Biden and don't think he's done a bad job, but he is fundamentally too old to represent the future of the Democratic Party. Actually, I'm sure it was another metric of Dubya's fundamental incompetence that he didn't dump the big dick Cheney in 2004.
I actually think the most powerful V-P pick would be a progressive or even liberal candidate--from the OLD Republican Party. Someone who switched to the Democratic Party precisely because the GOP is no more. The dominant rightwing clique of the neo-GOP is actually strongly controlled by the Reagan Republicans who used to be Southern Democrats. Unfortunately, I can't think of any examples of a prominent Republican who has switched to the Democratic Party. The neo-GOP party discipline puts Lenin's Bolsheviks to shame.
By the way, I don't think Reagan deserves much of the credit (or blame) for remaking the GOP into the far rightwing neo-GOP. That was mostly a negative reaction to LBJ's civil rights legislation, and Reagan was just an excuse that the Southern Democrats were waiting for. Almost any excuse would have done, and it was more like a supersaturated gas that suddenly condensed from gaseous Southern Democrats into Reagan Republicans. When I arrived in Texas in the mid-70s, there hadn't been a Republican governor of Texas since Reconstruction, but since the cloudburst of Reagan Republicans, there are no prominent Democrats in any statewide office in Texas.
Unfortunately, as much as I respect President Obama, I think he lacks Reagan's skills as a propagandist and figurehead, and that is apparently what it takes to motivate Americans these days. Or maybe it's just the superior power of negative motivations? The Southern Democrats REALLY hated LBJ's civil rights laws... Maybe Obama could motivate a large migration of old progressive GOP voters into the Democratic Party, but I haven't seen any hint of such a trend.
In conclusion, I repeat that I think it's time for Joe Biden to step down as V-P. Though the original article dismissed him as regards State, I think he could and probably would do a good job there. However, I think that Clinton has done quite well there and he would probably be overshadowed for just that reason, barring some massive success such as peace in Israel.