Today, it seems obvious for a superhero to be punching Hitler on the cover but what were attitudes of the US when Captain America debuted (in a comic with a March 1941 cover date)? Was that cover seen a confrontational to Nazi sympathizers and isolationists who didn't want the US to get involved in WWII? Was that a big statement when it was published?
Captain America Comics #1 was cover dated March 1941.
While the United States was not at war with the Axis at this time, the war was in full swing and Winston Churchill had recently given his famous "Give us the tools" speech, pleading for additional support from the US. (1)
One national survey the year before (1940) had found that 67% of respondents believed that a German-Italian victory would endanger the United States, and that 71% supported "the immediate adoption of compulsory military training for all young men". (2)
Individual Americans were volunteering (illegally) to fight against the Axis powers in other nations armed forces. One example is the three "Eagle Squadrons", fighter squadrons of the British Royal Air Force (RAF) made up of volunteer pilots from the United States which were formed between September 1940 and July 1941 and which flew in the Battle of Britain. (3)
Sources:
http://www.winstonchurchill.org/resources/speeches/97-give-us-the-tools
"What the U.S.A. Thinks". Life. 1940-07-29. p. 20.
"Eagles Switch to U. S. Army". Life. 1942-11-02. p. 37.