The simplest way to do so would be through the UI of course. Next would be temporarily disabling Steam Cloud for the game while playing. This method though leaves you with the game open, which could be it's own mess. Could also theoretically cause the save to fail to be written, but I've never had/heard of that.
This will cause Steam to 'crash', and may corrupt some internal configuration data and cause loss of settings ranging from the categories you've applied to client settings. Next would be force closing Steam rather than exiting it normally.
The easiest way would be to play in offline mode, provided the game is capable of that as some games will not be.
