The introduction of EFIS back in the late 1980s was a problem for older pilots who were used to stream driven gauges. Together with fly by wire, it proved too much for a few who couldn't hack the transition.
These days, everyone is used to glass cockpits so it's basically ECAM handling and the flight control systems together with the Airbus philosophy that needs to be learnt. The bus has lots of built in protections if you get things wrong and I would say that going from Airbus to Boeing and losing much of the safety net would be quite challenging as well.