I have been to Lago Como twice. I had a car both times. There is, however, a railway line from Milano to Switzerland up the east bank of the lake.
On my first trip to Lake Como (Nov 2004), I arrived by plane in to Bergamo airport. I stayed on the east bank, in a village called Varenna. Varenna has a railway station. Parking was limited and controlled. I parked the car on the road south of the village. We didn't really use the car other than getting to and from Varenna. There is not much to do in Varenna but there were some nice restaurants. We took a hike up the hillside from there to another village one of the days....it was hard work and I was a lot fitter then. Also had a day trip to Bellagio and day just pottering around in Varenna. Stayed in a hotel that had a small balcony and had lake views. It may have been Hotel Olivedo.
Most recently (June 17) stayed in Ossuccio on the west bank. Nothing in Ossuccio really. We stayed in a flat that we found on airbnb. It had a garage for off-street parking, which was essential. The roads through the west side, at times, can be very narrow to the point that two cars cannot pass. Italian (presumably) moped drivers must have very cheap life insurance. The driving was not relaxing by any means. We largely walked in to Lenno for meals. There was a very reasonable pizzeria (€7 for a pizza) and we ate there twice. At times, there were no pavements, especially where the road was narrow, so you had to be a bit brave, especially at night time. There was also an excellent gelateria in Leno. Our apartment was excellent, but would probably have preferred to stay in Lenno. Parking in towns was easier in the evenings but still tricky. We drove to Switzerland to go to a chocolate factory. At the Italian/Swiss border you need to pay €40 highway tax......it apparently lasts a year but you have to stick it to your car windscreen, so you won't get much use of that if hiring a car. And don't buy chocolate as souvenirs in June.....it will melt before you even get it to the car!. Lugano (in Switzerland) was a nice town/city.
You can take the water buses from Lenno and Varenna to visit other parts of the lake.
Como is the largest town and rather industrialized and not the most scenic of places.
The palace where Casino Royale and one of the Star Wars films was filmed is between Ossuccio and Lenno. George Clooney's villa is apparently about halfway between Ossuccio and Como. There is a rather upmarket/expensive drinking establishment, called Harry's bar, near there. Apparently George pops in for a cheeky cocktail.
Mennagio and Lenno would probably be the places that I would recommend you stay, if you have a car. If public transport, I would recommend Varenna.