I’d say atleast a year at a major in the right seat, one cycle of all the seasons actually flying in all the seasons would be sufficient. But some are upgrading prior to that, again all depends on the situations they felt with at their prior 121 job, and how those situations were handled.
Regional CA is essentially a checkairman job without the pay at this point, so when you upgrade at a regional, you better get the big picture hat on while keeping that right eyeball locked in on the person next to you if you don’t want to fill paperwork out. If you make it through a cycle doing that, I’d say left seat at a major won’t be too bad of an adjustment.
Now I’m only the right seat, but as far as difficulty, this major airline job has been the easiest job in my career by far. The resources we have to do our job are more than enough, the duty days aren’t too crazy and the experience level seems to be decent all around as a pilot group. If available, I’d take an upgrade tomorrow here.