There is an argument going around, mainly on the Left, that the Supreme Court cannot overturn the PPACA (aka Obamacare) because it is just too major and significant. It's sort of OK to overturn minor legislation at the margins, but if Congress does something really big, it deserved the Court's respect and acquiescence.
But it strikes me that the larger and more comprehensive a piece of legislation is, the more likely it is to run afoul of Constitutional restrictions. And this is the case no matter what theory one holds about the Constitution.
I am not a Constitutional scholar nor a lawyer, but I would describe two schools of thought on the Constitution. The first is that the Constitution gives the Federal government certain enumerated, defined powers beyond which it may not stray. The second is that the Constitution gives citizens a number of enumerated, defined rights (e.g. First Amendment freedom of speech) such that the Federal government can do most anything it wants as long as it does not trample on these defined rights. (I would argue that the first interpretation was the clear meaning of its authors, and the second interpretation is probably the majority view today of average Americans today).
But under either interpretation, larger, more sweeping legislation is more rather than less likely to cross a boundary that circumscribes Federal power. Whether such a boundary has been crossed by this legislation is another matter, but the argument that large legislation per se should be exempt from the possibility of being overturned on Constitutional grounds does not hold water.