Fundamentally, nullification makes no sense because it embeds in the Constitution the means of its negation by each state as it pleases. Of course, the supremacy clause means that the Constitution is supreme, not necessarily that the federal government is supreme.
It was the States that created the federal government in the first place. NOT allowing them the ability of nullification is like someone having a child and then letting the child run the parent.
It against the Laws of Nature. 'That which you create, you have a right to control' is a very old legal adage.
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Of course, the supremacy clause means that the Constitution is supreme, not necessarily that the federal government is supreme.
Which is also quite true.
The problem is that without nullification, the supremacy clause leads to the result of MAKING the federal government supreme, as the State cannot stop an unconstitutional act before it's implementation.
It is forced to drag the issue through the courts only to have it finally arbitrated by (you guessed it) the federal government itself.
In a nutshell, nullification is what was SUPPOSED to allow the States to keep the feds from rigging them system.