The US Navy did explore the concept of heavy four-engine flying boat bombers in the mid-1930s, commissioning designs from Sikorsky (XPBS), Consolidated (XPB2Y) and Martin (XPB2M). Only the Consolidated made it into production as the PB2Y Coronado, and of the 217 produced most were used as transports or for maritime patrol, though squadrons equipped with PB2Ys (VP-13 and VP-102) did bomb Wake Island in February 1944.

Though flying boats could carry an impressive payload over long ranges, making them very useful as transports, deploying that payload as ordnance was more difficult. The vast majority of bombers had bomb bays in the fuselage but having large, opening doors in the bottom of the hull of a boat was generally a Bad Thing, so flying boats tended to mount their bombs underneath or inside their wings, or store them in the fuselage then winch them out to wings. All air forces found that it didn't matter how many turrets you mounted on a bomber, they were still vulnerable to fighters and flak, and with the inherent performance disadvantages of flying boats compared to landplanes they were at even greater risk so would hardly have been suitable for a campaign against heavily defended targets like mainland Japan. As the war developed the improving performance of carrier-based aircraft made the aircraft carrier a more potent and flexible offensive weapon, and for maritime patrol the cost and resource requirements of four-engine aircraft meant more territory could be covered by the greater numbers of twin-engine aircraft that could be procured for the same investment.

The concept was briefly revived post-war with the Martin P6M SeaMaster, a jet-powered flying boat capable of carrying nuclear bombs in a rotating bomb bay within its fuselage, but with limited budgets supercarriers and ballistic missile submarines were a better investment for the Navy and the P6M never entered service.

For the most part, heavy airplanes like the ones you mentioned were used as transport/cargo planes. From Freedom's Forge, by Arthur Herman (page 277) "Glenn Martin had taken the concept a step further with the JRM-3 Mars, a gigantic flying boat that could carry almost 100,000 pounds of cargo across the Atlantic Ocean-far above the reach of German U-boats." My source then goes on to talk about the Hercules H-4 envisioned by Howard Hughes which never saw combat but was twice that size. "Taking off from water like a seaplane, the Hercules would carry one hundred tons of cargo, or 750 men or a Sherman tank, over a transoceanic distance at 20,000 feet." Regardless, it appears that these cargo planes were only focused on delivering supplies across the Atlantic rather than the Pacific.

While the war department ordered prototypes of Hughes' plane, (dubbed the Spruce Goose by the media) they also required that prototypes be built out of wood due to aluminum shortages. They also didn't allow for any profit on the production of the plane. In addition to these complications, Howard Hughes was notoriously difficult to work with (picture Elon Musk); he skipped meetings and constantly redesigned planes mid production. The engineers involved with the project recognized in 1942 that it would take at least 4 years to deliver the final plane. His partners on the project abandoned the idea and the government ceased funding. Howard did manage to get the plane off the water in 1947 after personally financing the project at a cost of $11 million.

Unfortunately, my book source does not focus on aviation as much as the industry surrounding wartime production so any further commentary would be speculative.