Definitely stick to the newer hotels (1990s era and later) with good ventilation systems. I've stayed at the Venetian a couple times on non-smoking floors, and never noticed any hint of smoke; I imagine Wynn/Encore would be the same. Same for restaurants, shopping areas, etc -- completely non-smoking, though bars and clubs I believe allow smoking.
The casino floor is another story. The newer places have the best systems, but someone smoking at the same table or nearby machine will always be noticeable. And real non-smoking gaming areas are rare (many poker rooms seem to be non-smoking, and the occasional table). Not sure how old this link is, but it has a summary of each casino:
http://www.lasvegasadvisor.com/nonsmoke.cfm
The main reason for a non-gaming hotel would avoid having to go through smoke to get to the room elevators (again, some are better than others, even in the same complex -- Palazzo signs the walkway area as non-smoking and has some clearance, while Venetian it's not as avoidable). But if you're planning to do some gambling anyway, that may not matter.