I know it's outside, but I did once participate in a treasure hunt along the banks of the Thames going from North (Houses of Parliament), crossing using the footbridge opposite St Pauls to the South. Ended up in a restaurant in Southwark and we all got pissed.

That was good. And there's plenty of landmarks about which clues can be made up (eg how many roses on the outside of the newly constructed globe theatre?) and a lot can be indoors (eg St Pauls, Tate Modern,).
You could even do a tube based one where you have to get out at certain stops. For those who don't want to walk.
This is all rather assuming it would be London based, of course.