I've never been to Brno and I'm a little overwhelmed by all the hotel options. I'd like to stay in a hotel that is central and gives me good sense of what Brno is like. I'd love to know where locals tell their friends to stay when they visit, and why those areas and hotels are special. thanks!
Be as central as you can, then the whole center is in walking distance. It's not a touristy city at all and the very best of it is in the center.
Brno really doesn't have a lot of hotels worth staying in. If you're not staying long just keep it central. last time I was in Brno I stayed in the Grandhotel Brno - overpriced, overrated, much more a 3 star than 4 star feel. I popped in to check out the recently-acquired-by-Barceló Brno Palace, that's a whole level different: http://www.barcelo.com/barcelohotels/en_us/hotels/czech-republic/brno/hotel-barcelo-brno-palace/general-description.aspx
Mentioned in this answer: