I think Joe's age will be the biggest negative in the eyes of the voters. As much as I am a fan; I've always liked Joe Biden. He is definitely showing his age. The gaffes are an issue. But its not new; he has been prone to gaffes over his tenure in the Senate. And its not like Trump doesn't stay stupid shit all the time anyway.
From my perspective, I can't think of any other election where the VP pick is so crucial. More often than not, the VP is just the running mate. But in this situation, it is probably the most critical component of Biden's election campaign. So I hope he chooses wisely.