Flying via FRA and connecting to LH is by far the best way from SFO or LAX to anywhere in continental Europe - much better to get the long leg done in one stretch and then have a short hop. Even if there are directs from ORD or IAD, I generally try to do it that way. LHR is theoretically similar, but the onward connections are much less seamless.

The other direction, coming back via IAD or ORD puts you on a domestic single aisle plane for 4-5 hours after clearing customs. Uggh.