One of the pernicious problems in large-scale software development is cross-team coordination. Most large-scale Agile methods focus on product and portfolio coordination, but there's a harder problem out there: coordinating the engineering work.
Poor engineering coordination leads to major problems: bugs, delays, production outages. Cross-team inefficiencies creep in, leading to Ron Jeffries' description: "a hundred-person project is a ten-person project, with overhead." One of my large-scale clients had teams that were taking three months to deliver five days of work—all due to cross-team coordination challenges.