I grew up in Brighton, N.Y. outside of Rochester and Williamsville, N.Y. outside of Buffalo. I have always been interested in an around Lake Ontario ride. I have done part but never around the lake and it has been years ago. We live in Tampa, Florida. I would be interested in what route you finally decide on.
We'll probably be keeping a journal on cgoab. Mean time, watch this space, as it evolves.
I would think the ride from St Catherine's to Toronto may be a little dicey. I would stay close to the lake.
That's my preference although I'm still interested in local intelligence on that. I did find a route using Google Walking that seems reasonable. Starts in NOTL, crosses the Welland Canal in St. Catherines, at the bridge closest to the lake. Stays below the escarpment, south of the QEW for awhile, then north of it. Actually crosses the Burlington Harbour on the low bridge to the north of the skyway.
It seems that Route 18 out of Rochester all the way into Rt 104.
Something like that. This is the easy part. Other than possible construction surprises. This part of the country has plenty of secondary roads with light enough traffic and adequate surfaces. There will be one overnight before the border, which will affect routing somewhat.
I would cross the border, where I-190 and Route 405 join near Lewiston. (Unless you want to go further south by Buffalo or Niagara Falls)
I had been expecting to take the Lewiston bridge, because getting through Niagara Falls NY left me with a bad taste in my mouth last time around. But I recently learned of a good route to the Rainbow bridge. And I like the Rainbow bridge (for crossing by bicycle) a lot more than the Queenston/Lewiston bridge. It's much shorter, and it has a great view of the falls. I also have a sister-in-law in Niagara Falls, Ontario, but that would make a short day if we spend the night there. As a result, I'm undecided.
I'd pick up Route 81 into St. Catherines and continue until close to Dundas. Pick up Route 8 then turn right onto Route 6 go over the Dundurn Bridge until you get to Route 5 or Dundas Street East and turn right. At this point, you probably have an idea what you want to do.
Actually, unless I hear a good reason not to, I'm thinking of taking surface streets that parallel the QEW on the north side through Stoney Creek and Hamilton. There's some parkland, and the rest of it is upscale housing along the lake front.
If it were me, I would turn right onto Route 1 or Guelph Rd. and take it to Route 2 or Lakeshore Road. Turn left and follow that through Mississauga and into Toronto. It parallels The Gardner Expressway so you may want to divert a little and explore Toronto. However I would get back on the Route 2 near Oakridge which becomes Kingston Road.
Here, my default is just to take Hwy 2 right across to the other side of Toronto and beyond. I suspect there may be places where that is non-optimal, hence the query.
I would take Route 2 east towards Pickering as you get near Oshawa it is still Route 2 but now is called King Street West. I believe Oshawa is the halfway point. You will continue east on Route 2 towards Coburg. It will go under the 401 near Coburg. Going east towards Trenton. (CFB Trenton Air Base is there) Continue east to Belleville. At Marysville it joins Route 49 but soon continues east again heading towards Greater Napanee and on to Kingston. It is east again towards Ganonoque and to the intersection of Route 2 and Route 137. Turn right onto Route 137 and head south towards the border.This is where I am not sure.
There is a double ferry trip. One to Wolfe Island from Kingston, another from Wolfe Island to Cape Vincent. Takes about 50 miles off the route, and avoids the nasty high bridge for 81. Assuming it's even legal to cross there. Google Walking adds another 50 or so miles to take the next bridge down the river.
I think you can cross back into the US by Hill Island. Pick up County Rd. 191 south on Wesley Island into the state park. When you get near Westminister Park Rd., you might have to get on I-81 to cross the bridge near Collins Landing. (After all, you are in the Thousand Islands) Get off I-81 as soon as you get near Route 12. Head Southwest on Route 12 towards Clayton, N.Y. In Clayton you want to take 12E. Take 12E towards Cape Vincent. Take 12E towards Chaumont. Continue towards Limerick and turn right onto Route 180. At Baggs Corner turn Right onto Route 3 towards Westcott Beach State Park. You will be on Route 3 for awhile passing through a number of parks. After you reach Selkirk Shores State Park keep an eye out for NY Route 104B, when you get there, turn right. Take that towards New Haven. It will dead end at Route 104 and you will turn right. Head towards Hammonds Corner and west to the lovely town of Oswego.
At this point we're in familiar territory. I've lived here for 20 years, and been up to the Watertown area probably 20 times (via 104/104B/Pulaski). So the whole Cape Vincent to Sodus is very familiar by car, will need some tweaks for bike, but not a lot. From Sodus on we're talking regular rides from home.
At this point I would take Rt 104 west near Wolcott, (or you can stay near the shore) the road with still be Rt 104 but it becomes Ridge Road East, but you of course will be heading west. Head towards Sodus and west of Sodus the Williamson Sodus Airport and continue west until you get to Webster. Almost there, continue on Rt 104 Ridge Road East until you cross the bay and into Irondequoit. Then you will be near home in Rochester. I can not speak about places to stay and sites to visit.
I know this was long but I believe it is as safe a route as you can get, unless you fool around with side streets. Considering you will be in some very densely populated areas between St. Catherine and Toronto, be extremely careful near Toronto. There have been a number of pedestrian and cycling deaths. I think the drivers there are worse than the one here in Florida and that is pretty bad. Good luck with your trip 
I've lived in Toronto. Don't know about the drivers being worse, but there are a lot more of them. Over 8 million people in the GTA (greater Toronto area), which is about half of the entire State of Florida. And that doesn't count Stoney Creek/Hamilton/Burlington
