The only person I ever saw who did exactly this format successfully was Michael Parkinson. And the musical item usually at the end was often one of the guests.
To make it work, you need to take risks. Here in Australia, we have a late night talk show called [link|http://www.rove.com.au|Rove Live]. The host's name is actually "Rove", hence the name of the show. He's actually a stand-up comic and does a few minutes of this at the top of the show. Then he has a few guests, interspersed with segments involving the show's "live" reporters doing things, usually with viewers. Sometimes he just sends a crew for a Rove Live Challenge (example: one girl had the show's hour to get as many people in her street as possible to change into Rove Live t-shirts.) Sometimes the guests participate in silly games, often he has a wierd local or something (a few months ago he had a 4-year old Elvis impersonator!) and usually has a mail-in segment called "What the...?" Then Rove ends with a band.
This basic format is a pared down version of what the venerable Hey Hey It's Saturday used to do every week for more than 25 years. Except they had two hours, more regulars and felt much more like a older variety show format. And was correspondingly more expensive to produce, which is why it isn't on anymore.
The other extreme is a show called The Panel which has a number of well-known Aussie comedians who sit around a table and talk about current events. They have guests for some of the show and sometimes have a band. But it's still the same type of format. In truth, they were surprised the network let them do it, but someone saw the potential and it's a ratings winner for Ten.
Somewhere off to the side is the format you described, sans the music, but with a distinct topic. Many of the programs on [link|http://www.abc.net.au/rn/|Radio National] work that way and the ABC has a few TV programs along the same lines.
I guess it really depends on the personality of the host(s) and the creativity they put into the format.
Wade.