That's a difficult one. If it was up to me I'd rather have some kind of federal republic with more power to the regional goverment - something akin to the US organization- probably with some sort of constitutional clause specifying how and when can member regions secede.
In a strict secesion or not secesion poll, assuming it was held today... I'm honestly at an impasse, as of late. A few years ago I'd probably have leaned on "no" (again, I'd accept secession after a poll if it came up. Better that than a military intervention to trump the poll results, as that general posted on his blog. This *is* my land and that of my ancestors since heck knows when, I'd rather have it remain prosperous, and not turn it into a war-wrecked ruin).
Nowadays I'm less sure on what I'd actually write on the ballot. My "no" on that came from a belief that nations were tending further and futher towards unification and supranational states (EU, et al), which I saw mostly as positive, and that going the other way around was just swimming upriver. However... the crisis, and the events during it, have led me to have doubts about this. And from there, having doubts about my usual position about what would. I honestly don't know which way I would swing nowadays. On one hand, I know that it doesn't address the root of the problems in today's society, and in this day and world nation states prosper or not depending on the whims of great financial blocks. On the other hand, looking around the disastrous management elsewhere it feels tempting, at times. Plus, meeting with people from other regions and hearing their thoughts and ideas about how life in the Basque country, which are quite odd and not infrequently border on the offensive... really, hearing someone who grew up less than 100 km away from my home city spout bizarre stuff about how he thought things were around here, and what kind of policies should be enacted... it does make you wonder.
The matter is complicated further by the complexities of nationalist politics around here. Simplifying things a lot: there's not a single common root for all nationalist parties, but three, each of which is stronger in one region, has it's own offshoot parties, and it's own love-hate relationships with the two others. But that's another thing altogether.
So, TL, DR: it depends on the circumstances in which this was called forth.