If there are even only say 100 Amerika-Bombers deployed for that purpose, if we assume they get through and get back every time, of course there might be thousands of raids. But first of all, while we don't want to get too bogged down technical hairsplitting, is it or is it not possible for one of these bombers to fly all the way to the US northeast coast and return from a base in say Brittany? The main reason I doubt it is that this sort of capability was what the USAAF was going for with the B-36, and yet that mighty bomber never did become operational before the end of the war. Even the B-29 was sort of an interim patch job--and could a B-29 based in Philadelphia, or even Loring, Maine, reach Brittany and return?
Staging through the Azores, I have little doubt the Germans could make planes that could do the round trip. But staging through the Azores, if we even grant they could do it once, is a one-time stunt. If they rushed they might get a few more sorties in, before the RN and USN converged on the islands and at the very least neutralized them by shooting down planes of this type--more likely, the Allies would have the power to spare to take them completely, especially because the Germans, who might perhaps get away with using them covertly, could never reinforce them with troops and defenses without tipping their hand and triggering a belated preemptive invasion by the Allies. They cannot be strongly defended; Portugal does not have the means to do so. And anyway Salazar's only prayer of avoiding blockade and being deposed at the least once the Allies win is convincingly pleading ignorance. He can't fortify the Azores even if Hitler gave him all the men and material to do so on a silver platter.
So if the shorter range from there is key, then it can only unlock the door a few times before the Allies change the locks.
Now then, if the Germans are forced to stage out of their continental holdings instead, bases in Brittany are the best of a bad lot, and I am very skeptical they can make planes that can deliver a serious bomb load and then make it all the way back to France. This means that each and every Amerika-bomber made and sent on that mission can only do it once, then a relatively short flight east to a waiting U-boat to save the crew (perhaps, parachuting into the Atlantic is pretty dicey). So if the Germans make 500 and use them all for this mission, that's a grand total of 500 bomb loads.
If that is the Americans never actually do anything about developing an interception system. I suppose OTL our continental defenses were a joke, because we darn well knew if we couldn't build an intercontinental bomber yet, neither could Hitler or Tojo. And anyone more thoughtful, who might question the premise that Yankee aviation was automatically at the very cutting edge and would not be surpassed in any way by any foriegners, would either be mocked and derided for lack of patriotic confidence--or taken quietly aside by other thoughtful people, who would point out as I mentioned above, that the Zeppelin raids were in themselves pathetic, but they forced the British to spend a lot of resources and men on air defenses, diverted from the battlefields of the Front. And that the London Blitz hardly brought the British Empire or even just England to her knees, nor for that matter were current British and American bomber raids looking to knock the Reich out of the war any time soon. So, if by some amazing demonstration of Teutonic technical prowess (or some stunt like aerial refueling--which would not be plausible to accomplish at this stage by the way) the Jerries did manage to put a flight of bombs over US cities--well, surely we aren't less capable of taking it than the British were, are we? So risking no air defense to speak of is a good way to focus what resources we could assemble first on the battlefield and toward victory sooner--and the sooner we win, the less possible a German air raid is.
But I would think that with the success of the first strike, that cold-blooded reasoning, that it is more cost-effective to endure bombing than it is to develop interception capabilities, would be quite silenced--indeed it always was silent, I don't know of any leader or speaker who ever said, folks, we are just going to take our chances here and see if Jerry wants to exhaust himself trying to blow up our cities long-distance. No one said that, no one ever would. Quietly meaning it would also not be tolerated however. Certainly not if a second bombing strike made it too...
After that, the President has to be seen doing something apparently effective to protect American lives. If the new Pentagon is willing to be brutally frank among themselves that a proper defense would cost too much, they still have to at least look like they are beefing up a serious defense, and politically speaking I don't think they'd dare do less than try for it properly. And although it would set back victory the USA can afford it. It would take time to deploy all the hardware and train up the radar teams and artillerymen and so on, but then again a lot of the hardware and troops were being developed for such duties in Europe or the Pacific anyway; someone might suggest it is good training before they deploy and a good place to rotate long-time deployed troops overseas back Stateside for their relief duty. This is the USA just as the WWII war machine was hitting its stride, and with substantial parts of the economy still held in reserve at that but convertible; for the sake of home defense you bet the home front will accept somewhat more austerity! The resources are there. Insofar as interceptors and AA can only have limited success in stopping the bombers from getting through, the defense will be a laboratory for improving those odds, and applying lessons learned overseas to further enhance Allied air superiority.
A lot of the German bombers then will either be shot down before crossing the shoreline, or diverted from their targets, or have their bomb runs spoiled, and then more of them will be shot down before their crews can ditch for recovery. And of course the Americans will figure that if these Jerries are not Kamikazes, there have to be U-boats out there to retrieve them, and they will doggedly follow the planes they can't actually shoot down to find these subs and take them out.
Really, if Hitler is serious, he needs either to somehow or other bring over thousands of Japanese Kamikaze pilots--not just pilots but entire flight crews of them--or else persuade his own Aryan darlings to accept an actual, no way out, suicide mission. And redesign the planes to take maximum advantage--no fuel reserves for a flight home, no bombardier--just sufficient flight crew to get the plane there and then for the pilot to simply find his target and dive the whole plane down into it, with said plane loaded to the gunwales with high explosive.
Such suicide missions might indeed not only expand the warload but make that warload count. I suspect that evading interception is much easier when the whole plane is the bomb and there don't need to be level bomb runs; it can come in jinking and make the Yankees guess what its actual target might be, and a damaged plane can divert to a target of opportunity instead.
An alternative might skirt close to suicide bombings with a fig leaf of technical survivability by planning to bring the plane in, most crew ditch, then the single pilot aims the plane at the target and bails out himself--if they survive, they surely will be taken prisoner by a nation that especially hates them of course. But would Hitler want to go to the trouble of locating a brave and capable set of volunteers, train them up, use them once, and then hand them over to the mongrel enemy? I'm thinking not.
Either it is frank suicide then, or the bombers will not be very capable of much load nor will they be able to target better than the haphazard, slipshod reality of American height bombers in this war. A mislaid bomb will probably kill somebody, but not the hundreds hoped for and not take out the targets most desired.
Also--even if we somehow have an Amerika-bomber with the range to get to New York, perhaps Philadelphia, maybe Washington DC--which means that of course all of New England is within its range too--still that leaves the vast majority of US territory out of its range. Because the northeast, especially the coastal conurbation, was so highly developed this small patch of the US (and however much of Canada it also can reach) counts for more than its geographic share. It can hardly be evacuated.
But anyway, most of the nation sits perfectly safe. Even places within the range of the bomber are sheltered if the bombers must first fly over defended territory. But even if they could level absolutely everything within range, and kill everyone resident or otherwise present there, the United States as an only somewhat truncated whole is right there, still fighting on and hardly impaired either.
The question of how many the Reich can build is one I wouldn't dare address, because it was never demonstrated OTL they could make even one successful prototype, let alone hundreds or thousands! Changing the goal to openly suicide missions would be a help, after the necessary redesign.