This is one of those hot button topics, but here is the skinny.
These days airline pilot time (part 121) is much more valuable to the majors than single pilot PIC in a part 135 operation. Sure, everybody and their dog will talk about a friend of a friend who worked at ABC freight and is now at AA or Delta, or X major.
Those are outliers who probably "knew" somebody. These days part 121 experience is gold and the majors are looking for it over single pilot time. This coming from various mainline pilots over the years.
I have also seen many friends of mine who flew for many years with various part 135 outfits (including Ameriflight) recently come over to Eagle and other regionals for this very reason. Their goal is a major and they figured out they need part 121 experience.
I would go with ExpressJet if that is your regional of choice. It is one of the better ones. These days there are only three,
maybe four regionals anybody should consider: SkyWest, Eagle, ExpressJet, and maybe Compass.
That is a different topic for a different time, but the following thread should be required reading for any aspiring airline pilot:
http://www.airlinepilotforums.com/re...yone-info.html
It takes a turn for the worse (and highly funny) on the third page starting with Reply # 27.