The NDP's announcement last year that they considered 50%+1 to be a sufficient margin to allow for Quebec separation caused controversy. Accusations that they had betrayed the federalist cause to the separatists were common. This is not quite right; the NDP have betrayed the separatist cause as well.
The primary claim of separatists is that an independent Quebec would be better off both politically and culturally. A 50%+1 victory undermines each of these claims. Even if the following is assumed to occur with the backdrop of a compliant Canada capitulating on every issue surrounding separation they still apply.
A Quebec state born from a 50%+1 victory would start its existence with a little under half of the population feeling it shouldn't exist. This does not bode well for stability. I suspect you'd quickly see separatist parties (or re-joiner parties) for Montreal and Northern Quebec. While some Quebec politicians have said Quebec is indivisible the hypocrisy of that line of thought wouldn't go very far with most people.
In a more subtle way 50%+1 undermines the belief that important decisions should have widespread consensus. The idea that you can ram major ideas through with the barest of majority support will lead to the kind of winner takes all attitude that plagues many new democracies (and some old ones for that matter).
Culturally, Quebec would have some immediate issues. Just as the referendums of years past led to an exodus of business from the province, a new Quebec state would lead to an exodus of those who don't believe in the new regime. While this makes the former problem less of an issue it does suggest a great draining of talent would occur. You
want as many people as possible to agree with any grand project before you set out on it. Its only common sense.
Given Quebec's recent issues with its immigrant population you can expect them to figure highly in the exodus. There are probably some short-sighted people who would see the immigrants gone as a good thing (more room for pure laine Quebecois afterall). Quebecers have felt their culture under attack for years but if your culture requires others
to leave in order to flourish its not much of a culture, now is it?
50%+1 would leave Quebec with a variety of internal issues not easily solved. Those who support it do Quebec an injustice.