1. I'm looking at midtown Manhattan, near fifth & Broadway, as a potential hotel spot. Is this an OK location?
5th Ave and B'way is pretty much where the Flatiron building is. Dunno bout hotels in the area. I imagine staying anywhere in Manhattan is gonna be expensive. The more touristy and trendy places even more so. Since I've never had to stay at any hotel in the city, I dunno what's reasonable/affordable. By "OK" if you're concerned about safety, then yes, it's totally fine. The only hotels I can think of are either in Time Square (and thus, probably hella expensive) and Chelsea (which is questionable - it's a gaybourhood, so it's reasonably safe, I just don't know much about the hotels themselves).
2. I'm trying to get the balance right between fair weather, not too busy (ha! Damned tourists who aren't us), and preferably no hurricanes, which may or may not affect said trip (sorry if I'm being ridiculous here, but apparently the risk exists, even though I don't hear much about actual hurricanes in New York) and am leaning towards late September, but want to check this is not a bad decision. With these three factors in mind, which would be better - late September or late October?
We don't get many hurricanes much. Although, supposably, we've gotten rain due to the storms around and about (Ike and such). This has been a strange summer for weather. Up and down. And now that it's practically fall, it actually was kinda hot these past few days. It's getting cooler now. I say either/or would be fine. It will be chillier in Oct, but if you're around here in late Oct, then you might be able to check out Halloween related events. Weather has just been really weird here lately. Last fall/winter, we had like these torrential downpours. Our streets were like totally flooded. This one day, the lil sis and I had to stay home because the traffic was so bad, we couldn't even get to the train station.

I blame global warming and Al Gore.
3. We will be going for a fair bit of Cultcher and pretty architecture, among other things. If you were to pick the top ten attractions for us to visit, what would they be?
I think you should definitely check out the typical stuff, like the Empire State building, Ground Zero/WTC, Times Square, Central Park, South Street Seaport. Don't bother with the Circle Line. Just head downtown and take the Staten Island Ferry for free. Definitely check out the Statue of Liberty/Liberty/Ellis Island if you can/if it's open (I dunno what the status of it is now, whether it's still closed or not). You could also check out Rockefeller Center, the UN building, and Grand Central Station.
For museums, I like the Metropolitan Museum. I could spend days there. But if you like more modern stuff, there's the Moma. If you like quirky installation stuff, there's Guggenheim. If you like artsy fartsy gaudy stuff, there's the Frick. If you like sciencey stuff, definitely check out the American Museum of Natural History and the Hayden Planetarium.
4. I am going to find knishes, come hell or high water. Where do you think should I go?
Yonah Schimmels Knish Bakery
5. Where would you recommend for:
a) Pizza
Lombardi's
b) Italian in general
Carmine's
c) Steak
Smith and Wollensky
d) Southern food
e) Mediterranean
I'm not sure if this is considered Mediterranean... probably not. It is more Middle Eastern/Moroccan.
Salam
But it is one of my and teh hubby's favoritest restos. I'll have to think about those other options. I don't think I've really eaten at any "southern food" restos that I can recall. If by "southern" you mean like cajun/ethnic style.
6. Any other places you'd recommend food-wise? Any nice but not too crowded bars for the slightly nervous tourist?
Food Wise
Klong - Asian
Panna II - Indian
Mama Mexico's - Mexican (duh

)
Harry's Burrito's - Mexican (cheaper, and great, really large Margaritas

)
Bars
Bar at the Maritime Hotel
Uh... I'm not much of a bar person. Lol >.< I may have to get back to you on this, as I can't think of any right off the top of my head.
7. Got any other suggestions for us?
Check out the west/greenwich village for shopping. The gaybourhood from like West 4th St. and 6th Ave to Christopher St. and 8th Ave is cute to walk around.
You might wanna walk around Wall St. just to see what it's like. Lots of tall skyscrapers and business suits and such.
In Central Park, check out the Shakespeare Theatre and the Great Lawn. Also the Carousel and the Boathouse might be interesting.
Chelsea around 23rd and 8th (the other gaybourhood I mentioned) has some great little restaurants, gaybars, and shops too.
The East Village has lots of divey, low key (but increasingly yuppie trendy) bars. Although alphabet city and the LES (Lower East Side) is really sketchy, especially at night. You know you're in alphabet city when the avenues become letters. Avenues run north and south in Manhattan, from like 11th Ave (West side) to 1st Ave (East side), and then they start turning into letters (Ave A, B, C, etc.) Generally... the higher the letter, the sketchier it gets. >.< I've never been further past Ave. C myself.
You may wanna also check out Chinatown and Little Italy, which like right on top of each other. I just remembered, they have an Annual street festival called the
San Gennaro Festival, which is running now until Sept. 21st. Lot's of great food. But if you miss it, they sometimes have random street festivals in the city in the chelsea/west village area.
Also, if you come for October, there's the annual
Halloween Parade in the Village. So you should try and check that out if you're around then.
If you're into churches, you might want to check out St. Patrick's Cathedral. And you may wanna take a look at
Avalon (FYI - club music will start playing, you've been warned

). It used to be Limelight. They remodeled the inside tho, so it's not as awesome as it used to be (in my not so humble opinion). A very popular club, mostly gay on Saturdays/weekends, but I think Fri nights were like the straight nights. It looks like a church from outside, and
Lenny Kravitz filmed one of his videos in there.
If you plan on taking in a Broadway show, you should check out the TKTS booth in the middle of Times Square. You show up early, the day of, like a few hours before the actual show, and see if you can get discount tickets, as much as like 50% off. Some shows, like Rent, allow you to show up about an hour or so before showtime, and you can stand in line for a raffle. I'm not sure if it's students only tho. But they raffle away front row seats.
Anyhew. Hope this helps and hope you have a fun and safe trip.
Ste