"The question is as old as the republic: How far can states go in substituting their own laws for those of the federal government?"  I thought that question was answered with the gay marriage approval by the Supreme Court.

"Nullification" of the Defense of Marriage Act and the numerous States' laws, including Oregon, who  had voted or legislated against gay marriage were nullified by the Court.

The short answer is, it depends on the personal opinion(s) of at least  5 of the 9 Supreme Court Justices as to which State or Federal laws are nullified and why.

The opinions and laws of State legislators, Governors, or the voters are subject to the whims of five Supreme Court Justices.