Wow... that's a lot of territory to cover! It's been a few years, but I used to run a 40,000 sq. km field study in eastern Ontario... let's see if I can jog the memory. Coming up I-81 means you'll be crossing east of Gananoque. Once you get into Ontario you'll be heading west to get to Prince Edward County. Rather than heading up to the 401 I'd recommend taking the Thousand Islands Parkway. It follows the river and is more scenic (although slower) than the 401, which is basically like an interstate hwy. There's an old Amish church if I remember correctly in Rockport. Cutting through Gananoque you can stay on Hwy 2 which will keep you close to the river and the old road into Kingston. Kingston is an interesting city with a lot of historic architecture. Limestone buildings everywhere. I remember the first time I was there I was driving along the river admiring the historic stone buildings until I came to one that was REALLY big. Took me a minute to realize it was the Kingston maximum security penitentiary. There are some great restaurants in Kingston, but my favourite by far is a Greek restaurant called Mino's. It's near the water, right by the Holiday Inn. Great food, excellent service, and the restaurant is filled with plants (not plastic ones). There are a lot of funky shops in Kingston if your wife likes shopping, and I remember it as a city where there are bicycles everywhere. Kingston is the southern terminus of the Rideau Canal, which runs south from Ottawa. It was opened in 1832, and originally built to provide a route from Montreal to Kingston (that didn't involve the St. Lawrence) after the War of 1812.
You can follow the water right out of Kingston, taking Hwy 2 to 33, which continues west. Just past Adolphustown the ferry (runs every 1/2 hour) will take you to Prince Edward County. The county is a peninsula, but it has that unique feel to it that islands have. Mostly rural, but there is a growing winery industry in Prince Edward County. You'll want to visit Sandbanks Provincial Park to see the sand dunes and the unique flora.
From there to Ottawa you'll probably want to take the road north to Belleville, then east on the 401. You can go east all the way to the 416, or if you want something more scenic you can go as far as Kingston and then take Hwy 15 toward Perth and Smith's Falls. This will put you in the Rideau Lakes area and the beginnings of the Laurentian Shield, which has some interesting topography. Perth is the site of Canada's last pistol duel. There's great bass, pike and muskie fishing in the Rideau Lakes, if you're into fishing. BTW, 'rideau' is French for 'curtain', because of Rideau Falls, where it pours into the Ottawa River. From Smith's Falls you can either head up to Hwy 7 and east to Ottawa, or go east along 43, through Merrickville and Kemptville to Hwy 16 and then north.
Ottawa is a city of parks, museums and government. Being the capital of Canada, the Parliament buildings are there of course. We don't even mind that Americans burnt them down (except for the Library), but it does get mentioned on the tour. My favourite restaurant in Ottawa is a little place called Chef Pierre. A little hard to find, but I like it. As far as museums there's the war museum, the science and technology museum, the aviation museum, the mint, the museum of natural history, the museum of civilization, the national art centre, the national art gallery... It's best to consider Ottawa and Hull together, although one is in Ontario and the other in Quebec across the river. The museum of civilization is in Hull, for example. Just north of there you get into the Gatineau region, and Gatineau National Park. There used to be (and may still be) a steam train that runs from the museum of science and technology up to Wakefield, Quebec. Sparks Street is a road that's closed to traffic, becoming an outdoor mall of sorts. I love the Byward Market downtown, and if you go there you have to stop for a Beavertail. Just ask anyone. BTW, if you're in the market and you run into Shingosi selling T-shirts, say hi for me.
There are a lot of trails around the Ottawa region, and if you go out on them, bring some sunflower seeds with you and with a little patience the Black-capped Chickadees will land on your outstretched hand. On one of Marcia's and my first 'dates' I took her out on one of these trails on an early morning in late October (26 actually - we were married eight years to the day later). It was going to be a sunny day but it was still cold and all of these eastern garter snakes were stretched out on the rocks trying to get enough warmth to move. I'd pick them up, coil them up, and stick them in the pockets of my denim jacket. When they warmed up enough they'd crawl out and go on their way. So here we are, walking along hand in hand with snakes crawling out my pockets and I'm thinking, 'This could work'. Anyway...
From Ottawa to Algnonquin you need to head west and north. Most people take hwy 17 to Renfrew and then go west on Hwy 60 from there. As you go through Wilno (Canada's first Polish community, I think), stop at the Wilno Craft Gallery. It's worth it. One note of warning: Renfrew county is pretty, but lousy for radio stations. CBC is your only choice up there, not that there's anything wrong with CBC! Finding your way is a little tricky, especially getting through Renfrew but you can ask people. It's also possible to take hwy 7 west to hwy 41 at Kaladar, then go north on 41 to 60 but it's longer.
NB: Hwy 60 goes through the south end of Algonquin Park and is the most traveled route. Whitney marks the eastern end of the park, and it's possible to drive straight through the park for free but if you stop you'll need a permit every day except Christmas day. There's another route into the north end of the park from Pembroke but if you're new to the area it's a lousy place to get lost (no cell phone service). Algonquin Park has several distinct eco-zones, all of which you'll encounter going down the highway. Algonquin Park has a very high population of moose, which are very big and very dark. If you're driving, especially at night, be careful as hitting a ton of moose meat is going to cancel your vacation. If you visit the Park museum, you'll come across a mount of an Algonquin Park wolf - a distinct subspecies. That particular animal was hit by a car and had her pelvis broken. She was put out of her pain with a .22 shell. I was there that night, working on moose ticks in the park when we got the call. Algonquin Park is big. I was working there in 1983, which I remember was the year of the invasion of Grenada. I remember that because Algonquin Park is 22 times the size of Grenada. If you're looking for a romantic place to stay in the park, I recommend Killarney Lodge.
West of the park you'll eventually come to Huntsville, which is at the junction of hwy 60 and hwy 11. To get to Tobermory (unless you have a boat) you're going to have to go south on hwy 11. AVOID THIS ROUTE ON FRIDAYS AND SUNDAYS!! It's the main conduit for cottagers from Toronto. BTW, just north of Huntsville is Burk's Falls, and 12km east of Burk's Falls is Pickerel Lake Lodge. I only mention it because Marcia and I used to manage that resort.
Huntsville USED to be a quaint little town, but it's become quite a boomtown with traffic from Toronto. The locals refer to the summer season as the time when the 'terrorists' arrive.
From Huntsville you'll head south on 11. You have a couple of choices as to how to get to Tobermory. On your way, if you stop in Bracebridge there's a restaurant with great blueberry pie, but I don't remember the name of it. Locals would know. Where was I? Oh yeah. One route is to get off 11 at Orillia and take 12 west to the 400. Then you take the 400 north for a bit to 12 again, and head west to 93, then north to 25 and west again. This sounds more complicated than it is. It's a circuitous route, but you'll hit some great beaches as you go - Balm Beach, Ossossane Beach, Tiny Beach, Wasaga Beach, etc. West of Wasaga Beach you hit 26, and that will take you through to Owen Sound. Owen Sound is the south end of the Bruce Peninsula. My brother-in-law's Vet clinic is there.
The more direct route is to take 11 south past Orillia to the junction with the 400 north of Barrie, the 400 south to 89, 89 west to Stayner and hwy 10, then 10 to Owen Sound. Not nearly as pretty though.
If you're camping, NNE of Wiarton (home of the famous 'Wiarton Willie' - the groundhog for Groundhog Day) is the Cape Croker Indian Reserve and there's a nice campground there.
The Bruce Peninsula is the northern end of the Niagara escarpment, and it has some pretty unique geology. It also has a remnant bear population and a lot of poison ivy, but I think I mentioned that already. If you get to Tobermory you could always take the ferry to Manitoulin Island, then you'll be able to tell people you visited northern Ontario as well. A lot closer to Tobermory is the ferry to Flowerpot Island - some really interesting geology there.
South down the 400 takes you to Toronto, and that's a vacation in itself. Toronto's a cosmopolitan city of over 4 million people and has all that you might expect. BTW, when you're driving down from Huntsville, consider that people commute to Toronto for work.
Anyway, any one of those places could fill its own travel guide.
Mike.