Yes, the city does pride itself on its architecture. I think you can tour the Frank Lloyd House. Frederick Law Olmsted designed Delaware Park. Downtown city hall has some architectural significance too, I forget what. The UB South Campus and Canisius College has some nice old buildings, but if you want to see (ugly) 1970s architecture, go to the UB North Campus where the Elliott Complex dorms were built to be riot-proof. There are some "cool" areas along Elmwood Avenue - we went to a newish place called "The Blue Monk" last fall. There is always the strip of bars along Chippewa if it's going to be a 4 am kind of night.
There are only 2 seasons in Buffalo, Grey and Summer. May would fall barely at the start of summer so you should be ok. You mentioned taking the bus to Fort Erie - if you are going to tour around Buffalo, you absolutely need a car. From NYC, Friday to Sunday will be more than enough time to cover Buffalo and probably even squeeze in a side trip to Niagara Falls (25 minutes away). Have yourself some chicken wings and a chicken finger sub and you can consider yourself a local for the weekend.