Be sure to stop by the Pitt campus and give Flying Frankie's regards to Mr. Pederson. 

Two Brothers BBQ.

Mt. Washington is a must, even if you just park on Grandview for a couple minutes to see the view. Eating at one of the restaurants there is a plus.

The Cultural District Downtown has a bunch of shows from ballet to opera to musicals to stand-up comedy.

Definitely go to Primantis. The original one is on Smallman Street in the Strip, and is open 24/7. Also, walk up and down Penn Ave in the Strip in the morning. It's full of awesome markets and breakfast spots. DeLuca's there is really good. Just get there early, because most of the shops close at like 3PM.

The Southside is the city's nightlife center. It's completely packed with 20-somethings on weekend nights. Think Court Street, if Court Street was 20 blocks long. A lot of fun shops and restaurants there too. I like Local and Nakama.

I'd avoid Station Square. It's nothing more than a tourist trap. I think it used to be more thriving, but now it's been reduced to Joe's Crab Shack, Hard Rock Cafe and other touristy chains.

I would just stay downtown if I were you. Traffic is hellish getting into the city from the suburbs

I concur with a lot of the advice here. Pittsburgh is a nice town with a really compact and pleasant downtown. If you want something historic downtown, the Omni William Penn is really beautiful. There are outposts of lots of other chain hotels downtown, and you'll get pretty much what you'd think from them. As to solid local restaurants (beyond the worthy Primanti's), I think Church Brew is cool, and there are a lot of good local places in the Strip and downtown. Some of my favorites downtown are Meat & Potatoes, Six Penn, and Olive or Twist. I don't get to Pittsburgh all that often, but it's a good place. Beyond downtown, I like Squirrel Hill (near the Pitt campus), but I don't know too much about other neighborhoods. The inclines are worth doing for the view and uniqueness. As mentioned by other posters, there are some decent restaurants up there too. Good luck.

It has been a while, but the Sheraton at Station Square is a good location, easy access to parking, a short walk from the trolley station, as well as the incline that takes you up to Mt. Washington.  Demand a room with a view of the river and downtown.

If you can get a deal (i.e. weekend rates) I highly recommend that you DO stay at the William Penn.  Even if it is pricey, it's very, very cool inside.  No cookie cutter rooms here.  The lobby and location are second to none. Their fitness center is one of the best I've ever seen.  You may not be a gym rat like me but drop in for the ambiance and the snacks.

Just my 2 cents from all the times I've been there:

    Everyone is talking about Primanti Bros but the one time I went there I was really disappointed.  So they put the coleslaw and the fries in the sandwich instead of next to it.  It's still a pretty mediocre sandwich to begin with and the coleslaw and fries are relatively flavorless and don't add much.  That being said it is a Pittsburgh staple.

    A much better staple in my opinion is The Original Hotdog Shop or "The O", on Forbes.  It gets regular TV mentions and is really tasty. Plus the servings of fries there are HUUUGE. Just get a small I'm telling you.

    In that same area if you are interested in college-y stuff then going into the Cathedral of Learning at Pitt is a must.  It's really pretty and historic.  Further, right there is CMU as well, which if the weather is nice is a pleasant walk around campus.  They have many nice quads and outdoor art etc.

    Unless you are into the 20s crowd I would avoid the southside.  Maybe doing something like dualing piano bar or something would be a more enjoyable night activity.

So I will take my turn since I am actually replying to this while in my office in Oakland and near downtown.

I don't know as much about you as others so I would ask if you have kids. If you do the natural history museum in Oakland is awesome and the science center on the north side is a must. The steelers don't play until that Monday night (11/12) which will be a bonus for you in terms of traffic and general drunkeness during the weekend.

I would head to the north side statdium areas (is that where you are staying?) as there are great restaurants like Hyde Park and Bettis's Grille. The Science Center is in that area as well and you can take a cab from there easily to the cultural district, South Side, Strip, etc. The strip has cool markets during the day and then bars at night (Eleven is a great restuarant but pricey).

I agree with above poster to avoid Station Square. UNLESS you want to go on the inclines up the mountain for the view or you want to take the kids (if there are any) on the Gateway Clipper boats that give a nice history tour up and down the rivers. You can also pick up the ducky tours there which are these bus/boat contraptions that go on land and water. Pretty cool. All that stuff starts and ends in Station Square but the bar scene sucks there. They even lost Pittsburgh Rare which was my favorite steak place.

I would also disagree with going to Permani's. Overcrowded, the bread on the sandwich's is flimsy so it all falls apart. Everytime. and all it is is turkey sandwiches with eggs and flies and slaw on it. Did I mention it is overcrowded? I'd rather go to a Max and Erma's actually.

Peter's Pub in Oakland near the University is the Browns' Backers' Bar (I'm from Cleveland). Walking through Oakland (cathedral of learning, Natural history museum, Schenley Park) is a lot of fun in the nice weather, but would be miserable if it is typical November weather so I would not go out of your way to get there.

And the real reason I would start on the North Side is that's where the casino now stands and you can end your night by losing a bunch of money! I actaully did well the last time I was there so I'm never going back.

Surprisingly a pretty nice zoo - if you like zoos.

Go to breakfast at DeLuca's 2015 Penn Avenue in the "Strip"  it is old Pittsburgh,  cash only. They give you a ton of vittles-not necessarily California healthy. 

Agree that Pitt campus with the Carnegie history is a place to go--Cathedral of Learning on Pitt campus only open for tours on Saturdays when class in session.

While near campus consider, Mad-Mex or Fuel & Funeral.

The view from Mt. Adams to downtown on a nice day would be top 5 scenic city scapes in the country.  

Walk over from your hotel to the Duquesne University campus and go to the Palumbo Center and see former Bobcat cager and coach Big John Rhodes, who is now an assistant there. 

And Monroe, you are in luck!  My OHIO son is in grad school at Duquesne and the Jazz Band is playing Thursday November 8th with a concert, "Jazz goes to the Movies" starting at 8 PM.  Impress your wife with a bit of culture and an inexpensive evening out--she'll be amazed you know people everywhere.  Just let the lead trombone know who you are.    http://www.duq.edu/academics/schools/music/calendar-of-events/november-events  to learn about it.