I have always heard that Jeb was the smart one in the family. Though of course when you listen to his brother it really doesn't take much to sound more intelligent.
To actually answer your question though...
Political ideology aside there is no legitimate reason that he shouldn't run if he wants to.
Having said that... The Bush family has already had two presidents. There is no reason that we should create the image of a "dynasty" by having a third. Secondly, I think the republican party would benefit by moving in a different direction and showing the country that they have more to offer than the same old song and dance. Then again, I think the DNC would benefit from the same thing.