What was the most significant argument of the
Anti-Federalists?

Lack of Bill of Rights

Explanation:

The Anti-Federalists were worried that a strong-central government would become a tyranny. The only way they were willing to ratify the Constitution was if the Federalists added a Bill of Rights.

An example of these rights were:

- Freedom of Press, Speech, Protest, Etc

First Amendment ^^^

a direct vote in which an entire electorate is invited to vote on a particular proposal. this may result in the adoption of a new law.