Once again, Williams doesn't seem to have thought this through very well at all. When one really looks at what he's suggesting, it represents a case of saving the Constitution by violating it.
Williams cannot possibly advocate that a state can ignore all federal laws they happen to dislike. The only reasonable interpretation is that he's suggesting that states have a moral duty to oppose unconstitutional acts.
Unfortunately, that raises some substantial Constitutional difficulties. No state is empowered by the Constitution to decide what is, or is not, Constitutional. That is a power reserved to the Supreme Court, under Article III. To bypass that enumerated power contradicts the point Williams seeks to make.
Suppose Congress passes Law X, and the Supreme Court rules that Law X is Constitutional -- which, under Article III, it is empowered to do.
Based on the Supreme Court ruling, the state's nullification action is unconstitutional: According to Article VI, the state's officials and judges are explicitly bound to uphold the Constitution, including this particular issue.
Thus, even if some particular attempt at nullification is morally justified, nullification is nevertheless an act insurrection against the properly constituted government.
The proper response of the Federal Government is of course open to question, and it's probably determined on a case-by-case basis anyway.
I think the problem here is that Williams has simply misdirected his ire. If there are problems with the federal government (and there are), those problems originate not in Washington, D.C., but in the states, and from the people of those states, from whence come the Senators and Representatives who pass those unconstitutional laws.
At root, the problem is a moral one. To quote John Adams: Our Constitution was made only for a moral and religious people. It is wholly inadequate to the government of any other.
Probably the best modern-day example of an attempt to nullify federal laws was George Wallace. According the linked Washington Post story: In September 1963, Wallace ordered state police to Huntsville, Mobile, Tuskegee and Birmingham to prevent public schools from opening, following a federal court order to integrate Alabama schools. Helmeted and heavily armed state police and state National Guard units kept students and faculty from entering schools. Following civil disturbances resulting in at least one death, President Kennedy again nationalized the Guard and saw the schools integrated.
Ironically, the motivation behind this particular nullification attempt is little different from what led the South to seceed prior to the Civil War.
There have been a lot of learned comments about the Constitution, the law, the courts, precedent, history and so forth. But those comments assume that the matters at hand are conclusively settled well within the bounds of a complex, ordered, more unified than not state of Society. However, these matters are conclusively settled closer to the boundary of the state of Society, where things are less complex, less ordered, less (if at all) unified.
These matters are conclusively settled when one side or the other reaches for a can of "WhipYerButt" and vows to open it and vigorously apply the contents. If the other side does the same, things can get nasty. By this point, one or both sides may feel betrayed (possibly correctly) and therefore justified (possibly correctly) in going outside the constraints of the state of Society to settle the issue.
Or not. One or both sides may decide that the benefits are not worth the costs. One or both may give in, or both may seek a way around the impasse. After all, balance of power is inherent to our system and this implies the occasional confrontation that doesn't lead to full fledge conflict. (And the can of "WhipYerButt" is always on the shelf. in reserve.)
It's not just a balance of power between the Executive, Legislative and Judicial Branches of the Federal Government. It's a balance between States and State Factions; between the national government and the state governments, and between the citizens and all the rest of it if the citizens care to exercise their power.
That begs the question of whether or not the citizens care to exercise their powers. Every time a jury nullifies, citizens are exercising their power. Citizens exercised their power (by showing utter disregard for the laws in question among other things) and the Constitution was changed and Prohibition ended. They exercised their power again during the Civil Rights movement, and legal interpretations and laws were changed. (Isn't this all a form of informal nullification?) And much if not all of this has happened closer to the boundary of the State of Society, not deeper in the interior.
The answer to the question of whether or not the citizens care to exercise their powers is "sometimes, if they see importance in the issue." The American people have been underestimated before. They underestimated each other at the beginning of the War Between the States, when each side thought it would be over shortly. Many, not all of the Japanese underestimated them prior to WWII. Bin Ladin and company underestimated them.
The country did not start out perfectly. However, we were given a foundation from which we could strive for improvement and not stagnate in the status quo. And some of us are always engaged in that striving. And when those who are engaged can convince enough of the others to join them, the bottom line is: "It. Don't. Matter."
What say you Mr. Williams?
Ms Coulter?