Looking at maybe riding US 2 east to west - either the whole thing (sort of through Canada), or picking it up just west of the Great Lakes.
It's basically October now and we wouldn't be starting for say a week - too cold to be pleasant? (I mean, I'm sure it's possible, but we are lazy creatures accustomed to pleasant rides...)
If it's not already too late, how late is too late? If you don't know for all of it, please feel encouraged to answer for specific bits near you or just whatever you are familiar with.
This has been a strange year weather wise in the upper great lakes area so all bets are off on what weather you can expect.
I have ridden the Canada to Wisconsin part of 2 many times in October & early November. You can expect anything from some snow, to frosty cold mornings, to sleet, to rain to sunny afternoons with great riding. (lots of dark shadows on the road this time of year)
Big issue in the upper great lakes this time of year is deer or bear on the roads (especially in the dark). Hunting season & cool weather makes the deer edgy & on the move. Not just standing on or along the road sides but darting across with no regards for traffic. (my biggest worry is not hitting the deer as I can usually mostly get around them but my big concern is an oncoming car or truck hitting one & flinging it high into me)
This is a beautiful time to make the ride across 2 (the earlier you get started the better as it can change fast this time of year) but unless you are in no hurry & can keep the travel times to daylight & sit out the bad weather then the suggestion in a post above to have an alternate southern route planned & ready is a good suggestion.
I can't comment on the more western parts of 2 this time of year so hopefully riders in those areas can fill you in on that part.