Train from Frankfurt Flughafen to Milan, Italy

I'd guess via Zürich would be the fastest route. But it is a pretty long trip so if i was to do it I would probably spend at least a few hours in Zürich to break up the trip a bit.

The railways' online booking systems, like Deutsche Bahn (bahn.com) are pretty smart. If you put in your starting point and your destination (even out of country) it will automatically show the most direct and fastest routes, as well as alternatives, including showing you the durations. So you don't have to try and figure that out on your own.

The trip is likely to be a bit faster next year as the Ceneri base tunnel that is scheduled to open in December should cut 30-45 min of the travel time.