Your definition of "very comfortable" must be very different than mine. I'm "very comfortable," but I'm also single with no kids and no college debt. Add any of those to the equation, and the comfort level goes down appreciably.
Frankly, my opinions on this have gone back and forth, which you could probably find if you did a search on my posts for the past several years. Currently, though, my opinion tends to lean towards the side of those who say to get the hell out of the regionals. The mainline managements have launched an all-out jihad against their regional feed, and no one is safe. Prospects for a decent career at a regional are next to nonexistent. Even if your carrier is still around in 10 years, the likelihood of the QOL and pay being something decent is incredibly low. The leverage just isn't there right now, and probably won't be, since the mainline carriers continue to shrink their RJ feed and replace it with mainline flying.
That said, I'm not telling everyone to jump on any crappy opportunity that comes along. Obviously, I'm leaving the industry because I don't want to live the lifestyle that you describe of commuting to Oakland and sitting reserve, no matter what the paycheck looks like. But if something decent comes along, don't pass it up because you're waiting for the perfect offer. That comfortable gig at your regional could be gone in six months, no matter how safe it looks now. And then what will you think about how you passed up an opportunity at Spirit because you were waiting for Delta to call?