Does this Italy/Switz itinerary seem reasonable?

Your timing does not raise any concerns to me. www.viamichelin.com can help with driving plans, usually more conservative than Google Maps.

If you take the full Bernina Express route, the once-daily bus connection from Tirano arrives in Lugano at 17:30. If you are planning to take local bus C12 to Menaggio on the same day, then the last departure looks like 18:46 in summer (estivo). Or you have the option to head south by train from Tirano to Varenna on Lake Como, if Lugano is not your destination; schedules on www.sbb.ch and www.trenitalia.com.

Friday Yes, that sounds doable.
Sunday That is the shortest route. I believe the bus may go through the Grand St Bernard Tunnel. Check and see if this is the case.
Tuesday Take the Golden Pass route through Zweisimminen.
Friday It will be a full day to get from Lauterbrunnen to Varenna on the Bernina Express route. Leave at 7:33 and get to Zurich and then to Chur at 11:22. At 11:58 train to St Moritz arriving 13:55, change to train to Tirano leaving at 14:48 getting to Tirano at 17:00. You have 10 minutes to get across the piazza to the Nord station for train leaving at 17:10 getting to Varenna at 18:37. Do not go to Lugano.
Sunday Train to Milan from Varenna. Its 1 hour.

Aha, I did not realize the train trip from Lauterbrunnen to Tirano would take so long. Varenna sounds like the place to stop, no Lugano for us! That will save some time. Thank you both for that suggestion. Laura, I will look at the Michelin link for driving advice. I'm a little apprehensive about driving in Turin, but once we get out of town I think we'll be fine. I understand that the drive from Savona westward is very beautiful and am looking forward to that.

grazie to you two!

I can comment on the Aosta - Montreux leg of your trip.
The road does have some pretty significant curves in it but it isn't a nail-biting, fingers-buried-in-the-back-of-the-seat-in-front-of-you kind of road with drop-offs on one side and no shoulder. It's quite wide and smooth and 4-lanes in many parts of it, sometimes going down to 2-lanes. I've driven this road several times and it is quite scenic.
I'm sure the route takes the St. Bernard Tunnel since the road over the pass is much longer. I've driven that one too and would not want to do it as a passenger in a bus!

I would look at spending less time in Turin and perhaps longer in the Alps and Milan
Turin (3nts)
Montreux (2nts)
Interlaken (3nts) I think this offers more options as a base to Alps, Lucerne, Bern.
Chur (1nt) You really have to overnight here to make the Bernina Express journey the following morning.
Bernina Express from Chur to Tirano, then bus to Lugano, on to Lake Como (2nts)
Milan (2nts) I think it warrants a full day to get a feel rather than just a few hours - do The Last Supper !!

Please post a trip report when you return. I'm interested in the Turin area & Aosta.

You won't want to leave the Lauterbrunnen area! You might want to check the train connections to Lake Maggoire vs. Lake Como. We took the train from Wengen, Switzerland to Stresa, Italy with a quick stop at Spiez for lunch - very modern train into Italy with great connections. (Less than 3 hours total.) And, it was difficult to leave Stresa, too! : )

You could possibly help logistics by limiting yourself to just the one crossing of the Alps (on the Bernina Express).
Turin-Milan-Como-Lugano-Tirano-(Bernina Express)-Chur-Lauterbrunnen-Montreux (Geneva)

Our plane tickets are already purchased to/from MXP. I had looked at the open-jaw scenario, but actually the round trip was cheaper by a couple hundred bucks. You all have given me great feedback and some things to think about. Whatever we finally decide, I'm sure we are going to enjoy this trip. None of us has been to northern Italy or Switzerland before and we are expecting to be awestruck by the sights. It's gonna be good...