Fifty dollar bills will probably be accepted at the larger hotels, airlines and probably tour/dive companies where your total bill might be more than $50. It's the smaller businesses that might not want to accept them.
In most of Belize, prices are quoted in BZ$, but in many businesses related to tourism, you will often see prices quoted in US$. Since the conversion is simple and fixed (2:1), there's no real need to quote in both currencies. If it's not clear whether US or BZ, ask.
Traveller's cheques have saved me on more than one occasion, and I still carry a few. Never found them to be more trouble than they're worth.