Like any other engineering artifact, airplanes are a product of compromises between design, mission profile, aerodynamics, flight dynamics, structures, powerplant, systems, maintenance requirements, airport requirements, etc. As it turns out, Jack Northrop was right: Flying wings and blended wing designs are the most aerodynamically perfect solution for subsonic heavy aircraft with an added benefit of a very low radar cross section ideal for military applications.
When I was an intern at Boeing in Everett, WA back in 2000, we considered the idea of flying wings for civil transports. While the aerodynamics make them very appealing to design and build, there are several added concerns that, combined together, deter further development of a civil transport in this configuration.
EASE OF ASSEMBLY - It is easier to assemble a semi monococque fuselage and wing box as opposed to a single, large wingbox with a cabin inside.
EMERGENCY EVACUATION - The biggest drawback to large scale flying wings is that they have less surfaces available to construct walk-in entry and egress doors, which makes it difficult to evacuate the aircraft quickly in an emergency situation. As a yardstick, an A-380 can evacuate a total manifest of 700 people in a few minutes but the fuselage also accommodates no less than 16 emergency exits equipped with escape slides / rafts to do this. Said number of exits are not possible on a flying wing, making it more difficult and dangerous to conduct an evacuation in an emergency.
EASE OF MAINTENANCE - Conventional airliners contain their engines and system in easily accessed compartments along the lower parts of the fuselage and wing or tailcone pylons. On a flying wing, these systems are buried deep into the structure where they are not readily accessible.
AIRPORT INFRASTRUCTURE: Flying wings are going to have very large spans, which push the dimensional limits of existing runways, taxiways, ramp aprons, terminal gates, etc. placing limits on routes to airports which can accommodate these aircraft. This has a direct effect on operational flexibility for the airlines looking to maximize optimal routes, large amounts of paying passenger traffic, etc.