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Let's assume (1) you can get hired and have received an offer, (2) it's a decent, stable company, one where you don't have to worry about being paid and which has a decent future, and (3) a place where you want to be.
Somehow, from the way you've phrased your question, I gather that you're not sure if you can handle it. Only you can make that determination. If all the answers are "yes," most certainly you should go for it. Such opportunities don't grow on trees; especially now, with little hiring, you never know if and when you'll get another chance.
The question is mainly as to whether you'd take a chance with a major right now and be a furlough fodder on the bottom of the seniority list at a major versus building your turbine PIC time and be safe from getting furloughed.
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.