Hi Alan,
Travelling north from Milan, both the Gotthard route via Chiasso and Belinzona, and the Simplon line through Domodossola to Brig are well worth considering, though you need to avoid the new base tunnels that both have, and use the old lines! The scenery is stunning in both cases, although if your wife doesn't like heights she may not enjoy the section from Brig to the old Lotschberg tunnel - the line rises very steeply on the north side of the Rhone valley, and at Hohtenn, before the line enters the Lonza gorge, there is an almost sheer drop of well over a thousand feet when you look out of the left-hand window! A benefit of this choice however is that it would be very easy to change trains at Spiez for the short lakeside run down to Interlaken for your overnight stop. From Interlaken Ost you then have the Brunig and other ng lines running into the mountains to be explored.
An alternative might be to change at Brig and take a train along the Rhone valley via Visp and Montreux to Lausanne. There is a really beautiful stretch of line right on the shoreline of Lake Geneva, and at Lausanne, rather than continuing to Paris via Geneva, what about a TGV via Vallorbe, Frasne and Dole? The countryside is pleasant rather than dramatic, often wooded, and includes the descent of La Bosse, a fearsome gradient (particularly in the days of steam - double-headed 141Rs, although a bit before my time, but only just!). Another advantage is that Lausanne is a lovely town with plenty to do. There should also be time to alight at Montreux and sample the MOB and maybe even the Blonay-Chamby preservation set-up.
Hope the foregoing is of some use, and I hope the two of you have a great trip.