If the "major" you are considering is hiring now, chances are you would not be "furlough fodder" on the bottom of a seniority list for long. Most of the majors/nationals that are hiring now (FedEx, SWA, JetBlue, AirTran, Frontier, etc.) will probably continue to hire, especially when the industry turns around, which I believe will happen, as historically has been the case.
If your goal is to work for a major, I would not turn down the opportunity to get a seniority number. If your goal is to work for a particular carrier and you need more turbine PIC time to either meet their minimums or to be competitive, then you have to make the decision that best suits your long term goals.
And if you believe you are ever "safe from getting furloughed" in this industry, you haven't been around long enough.