The single most important figure in the drafting, ratification, and short-term implementation of the Constitution was James Madison. A year or two into the Washington Administration, however, he effectively joined the opposition, which leads us to the Madison question: what happened to cause him to flip to the Jeffersonian side?
There are two plausible answers to this question. The first is that the mild-mannered Madison was intellectually seduced by Jefferson after the latter’s return from France; I believe there is a quote from Hamilton to the effect that Madison was always destined to be “a handmaiden to a greater mistress.” The second is that Madison’s enthusiasm for the Federalist cause was motivated by misgovernment at the state level, that he saw the federal government largely as a mechanism to check state excesses, and that Hamilton’s vision for the use of federal powers, when put into practice, went beyond anything he had imagined. The two are not mutually exclusive, and I think there is some truth in both of them, but would lean more towards the latter explanation.