It's pretty widely held that FDR had Joseph Kennedy in mind as a likely successor to be nominated in 1940. In OTL, Kennedy shot himself in the foot with his various pronouncements: various things he said didn't sit too well with the British government nor with FDR and the interventionist/internationalist segment of the Democrats.
How could Kennedy have gotten the nomination nonetheless? I suggest it would have taken a stronger America First / isolationist lobby: perhaps a public rapprochement involving Kennedy, Lindbergh, and Henry Ford might have done it. Had that happened, there could have been a double mass migration: hard-core isolationists like Republican senator Gerald Nye of North Dakota, or congressman Thorkelson of Montana would have crossed the aisle to support Kennedy, while interventionists might well have closed ranks behind Wendell Willkie.
In short: the personas of the two parties might well have reversed completely, or some of the more partisan types would have had to grit their teeth to support the standard-bearer (Herbert Hoover, for example, was of the isolationist ilk and was not completely comfortable supporting Willkie in OTL; I can't see him supporting Kennedy at all). That might well mean Wendell Willkie in the Oval Office on 7 December 1941, and a not very different course of action at all. But I digress.
Suppose the isolationists and America First types had carried the day, nominating Kennedy for president and Burton Wheeler of Montana for vice-president. Now you have a Fortress America believer in power, while Congress may be more up for grabs. Still, tensions with Germany might have decreased to the point where U-boats assiduously avoided American vessels. I can see where Hitler would have told Tojo to mind his manners with respect to the US; if the Japanese went ahead with the attack on Pearl Harbor, the reaction from Berlin to Tokyo might well have been "you're on your own". I don't think Kennedy would have had much of a problem with a largely-naval war against Japan; that had been part of the American psyche, especially on the west coast, for about 45 years already.
So what comes out of the separate conflicts?
I'm guessing a European continent under the grip of Nazi Germany with Spain, Portugal, Switzerland, and Sweden at least nominally independent (although behind-the-scenes Swiss collaboration with Hitler isn't out of the question, and we all know where Franco stood). Great Britain would probably have had to come to terms somehow, likely with Churchill's departure from office. Relations between the US and Great Britain would surely have been cooler than they were in OTL for at least a generation.
In the Pacific, I suggest the war would have lasted until at least 1947 if not into 1948: the intellectual firepower needed to produce nuclear weapons would have been spread out in both Great Britain and the US, with no collaboration. It would have taken either conventional weapons and a messy invasion of the home islands or a strangling blockade unto starvation to get the Japanese to surrender-or perhaps a combination of both. Sixty years later, Japan might still be recovering from the aftereffects of the endgame of this war.
The US today would probably be more xenophobic than in OTL, with tough immigration restrictions. I wonder whether Israel would exist as a nation: at least in the beginning there would have been little/no US support, which might have led to a mindset that would last for at least a generation or more. I suspect the US would have developed nuclear weapons on its own by the late 1940s/early 1950s; Great Britain would have probably developed them about the same time; Germany...guessing that nation might be close by now but not yet there.