Well, my take on it is that 121 PIC turbine, >20,000 multi-crew certified airplanes are the best time to try and get hired with a major. However, I know several people that have only had 135 PIC turbine time and gotten on at FedEx, Southwest, and UPS. If going 121 will take a long time to upgrade again, you're probably better off getting at least 1500 to 3000 hours of PIC turbine time.
However, if you have an opportunity to get widebody international 121 time and already have >1500 PIC turbine time, then that's probably better for FedEx and UPS.
Remeber to also think about what works best for you. If your hating the job or type of work, that's not good for anyone.
Best of luck!