Heading west on I-94 in Woodbury, MN is a BGS that says "St. Paul 7" . I was curious if similar examples existed since usually when you start blending into suburbs those distances stop appearing.
You can have your own definition of "major" but I'd expect it'd be something of regional or national importance.
Don't know if this would be too far of a distance, but on I-290 west, there is one that says "Worcester 13" (13 miles to Worcester)
North of Exit 16 on Interstate 81 in New York there a sign that says "Syracuse 2 / Watertown 74".