Advice Needed: Switzerland Road Trip 29 April-10 May

Google Map Option 1

Google Map Option 2

All depends on your preferences.
Option 1 is much faster (all by highway).
Option 2 is more scenic: you will be close to snow mountains and glaciers when you cross the Simplon Pass (road free of snow with a probability of about 98 per cent in late April, some black ice possible in early morning, however) and you will have fine views to Aletsch Glacier (longest glacier of Europe) as well as to some more than 4000 metres high peaks from the Pass. You can furthermore enjoy a panoramic view from Mont Blanc up to Matterhorn if you make the slight detour from Sierre via Montana - Crans s/Sierre - Ayent to Sion.
2 castles and oldest playable organ of the world at Sion. Roman theatres at Martigny and Avenches.
The road from Locarno to Domodossola goes through a romantic narrow valley and is rather slow.

Flights to London Gatwick from Basle, Zurich and Geneva,
to London Luton from Geneva and Zurich,
to London Southend from Geneva,
to London City airport from Berne, Zurich, Basel, Geneva
to London Heathrow from Zurich, Basle, Geneva
to London Stansted from Basle
check eassyjet, ryanair, skywork, swiss, british

Thanks - seems like option 2 has good scenery.

Any idea where's a good place to stay for the night between Milan/Lugano and Montruex/Lausanne?

Seems like a 7-8hr drive on paper from Milan to Lausanne, so would probably like to break it up, and stay for a night somewhere along Brig/Sierre/Mortigny.

Can I just decide on the day itself by turning up? ;)

I assume that you are aware that renting a car in country A and dropping it off in country B, causes a rather big drop-off fee.

Keep in mind what #4 writes about dropping off your car in a different country.

Between Milan and Lausanne Brig is a nice time for a break.

As for Alpine passes in Switzerland, this is a good link: http://www.tcs.ch/it/auto-mobilita/infostrada/passi-svizzeri.php?navid=181513181513, but the language choices are restricted to Italian, French and German. You shouldn't have problems with Simplon as mecker writes; last winter has brought heavy snow at higher altitudes.

Crossing the border between Italy and Switzerland is usually not a problem, sometimes passport are checked, often they are not.

Thanks for the tips and warnings.

I've taken the advice about picking up a car in Milan and dropping it off in Zurich. I've changed my plan so I pick the car up from Lugano and drop off in Lucerne - that saved me about $600-$700 CHF!

My refined plan:

Land in Milan - take train to Venice for 3 nights (3)
Take train from Venice to Lugano, where I will pick up the rental car, and drive to Domodossola and stay for a night (1)
I am contemplating if I should then drive and stay 1 night around Martigny or Montruex (1)
I intend to then stay in Lausanne for (2) nights, before....
heading to Berne for a (1) night.
From Berne, I will drive to Interlaken/Lauterbrunnen area and stay there for (4) nights.
Then it's (2) nights in Lucerne before taking the train to Zurich Airport, and flying out to London.

One questions though:

I have 4 nights reserved for Domodossola(1), Martigny/Montruex(1) and Lausanne(2) - I'm wondering if I can pull one night out of there and give it to Interlaken, as it seems like a very nice place to spend more time in.

Any recommendation which I should forgo?

Thanks!

Stay the first night in Switzerland at Lugano or Locarno. These places are much more scenic than Domodossola. I would spend less time at Lausanne and Interlaken in favour of the Valais. Spend your second night at Crans-Montana, the third one at Montreux and visit Lausanne as a day trip from Montreux or on the way to Berne.
People usually visit Gruyeres and Fribourg, may be Murten, if they go by car from Montreux to Berne
BTW: I suppose you could give back your car at ZRH airport too.