It doesn't take much capital to turn a 19th century mansion into an incubator/hacker house. Sure the weather and the Bills suck but inside you'll find a welcoming community spirit at a price you can start a business and raise a family at.
Buffalo has also been experiencing a boom in green tech investment (http://mobile.buffalonews.com/?articleRedirect=1&url=http%3A...)
As for Upstate NY in general, I think it's a great place to start a business. At the end of the day, most businessss can be run anywhere (hence the boom in remote work), and, again, putting aside the biblically shitty weather, you have an affordable region with plenty of fresh water and local farms, and isn't at risk for rising tides (NY,FL,CA), earthquakes (Cascadia,CA), droughts (CA, southwest, Midwest when the aquifer runs dry), name it. This is a great region to start a family, and at the end of the day, your best employees are the ones tied to your office and location, not mercenary college grads shopping around every couple years for a raise.
In 100 years, Upstate NY can exist without desalinated/pumped life support. Not so sure about the rest...