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Well it never hurts to visit new places. Stay downtown since that is our entertainment district. I can't help with the club selections since I don't go out partying down there anymore but check out Buffalo bar fly.
Coming from Toronto to Buffalo is a switch usually its us Buffalonians going to Toronto for the night life. Downtown is not the safest and its pretty dead after 6. I would recommend staying in Toronto as there really is no comparison. I have been to Toronto at least 100 times and I love it. Buffalo is more comparable to Hamilton.
Buffalo is actually a surprisingly good town for bars and nightlife. Last call is still 4AM, which is almost as good or better than most big major US cities. Chippewa is the nightclub strip downtown, it has something to offer for everyone. Allentown is the up-and-coming, hipster-type bar-hopping strip and the center of Buffalo's LGBT community. it has a very Chelsea/Grennwich Village-esque vibe on weekends. Elmwood Ave caters to the more upscale yuppie/college crowd but it's 2 straight miles of more bars, restaurants, clubs and lounges so it also has something for pretty much any preference. The most overlooked party strip is Hertel Ave east of Delaware. I personally liken it to Elmwood for a somewhat older (mid 20s to 30s and up). There are also nightlife clusters all up and down Main Street and more places pretty much sprinkled all over the city. Google Maps is your best friend in these kinds of situations as always
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