First of all with Ryan Air they want the Center of Gravity as far as possible to the rear border
.. but surely not at the expense of revenue .. other things being equal it would be silly to leave revenue behind provided the revenue outweighs the cost of increased fuel burn. More likely pax/bags will be left behind because the loading cannot be reworked to accommodate the available load within the weight and CG limits. It would be equally valid, commercially, to do so if the time delay were likely to cause subsequent schedule disruption or related costs .. eg in respect of curfews and slots.
Several considerations -
(a) with the same Type/Model/configuration/empty data .. then one aircraft should be the same as the next for loading .. vary any of the basics and you have different loading scenarios.
(b) no system gets it right all the time. Hence the best systems have a multistage approach to loading so that there are a few spots where checks and balances are expected to pick up on the screw ups
(c) the operating crew member who does the final check on the load is the final opportunity to detect a problem
(d) the best system I have seen for speed and accuracy involved ground personnel running up a trim sheet (doesn't matter whether it is manual or electronic) using company SOP loading and local flair. The crew then ran the final cockpit checks with the FO spinning a circular trimsheet prayerwheel and the captain calling the loads and running the totals. In the freight world this should also involve a crew member running an eye over the physical load (either as the cans are loaded or after, depending on configuration) and making sure that what the sheet says .. is what is on the aircraft.
(e) let your guard down and, sooner or later, you will have raised eyebrows or worse .. especially in the freighter world. Doesn't matter how good a stick and rudder man you are ... run the CG too far aft and the aircraft will give you a BIG surprise (I know of one TP who managed to get such an aircraft around the circuit and back on the ground) .. back a bit further and, with a dynamically unstable loading .. it is a guaranteed crash off the end of the runway ...