It can certainly happen, but it's nowhere near as likely today as in the early days of deregulation when things were still shaking out. It was assumed and understood that there would be post-deregulation casualties...

Now that we have three "super legacies", the loss of any single one would cause major economic disruption, especially during peak travel periods when there is zero excess capacity anywhere else in the system. The government would almost have to intervene. Even a modest sized major like US would cause enough disruption that Washington might save them just to avoid the bad press.

Regionals are mostly small enough that nobody will care if they go away, and they have the additional risk factors of competition, sudden contract termination, and getting stuck with obsolete airplanes.

A major with old (paid for) airplanes can limp along with them for quite a while. A regional which does not own a fleet of the "airframe of the month" can be rapidly kicked to the curb (see the comair thread for more details).

Also a less-than-competitive major can linger for decades, breaking even or losing modest sums...a regional in that same boat will only make it as far as the next contract renewal.

Odds of long-term stability are probably significantly better with a major (not including startups).