If you're on a Mac and have been wondering why /usr/bin:/bin:/usr/sbin:/sbin:/usr/local/bin keeps getting prepended to PATH when you run tmux, it's because of a utility called path_helper that's run from your /etc/profile file.
You can't easily persuade tmux (or rather, bash) not to source /etc/profile (for some reason tmux always runs as a login shell, which means /etc/profile will be read), but you can make sure that the effects of path_helper don't screw with your PATH.
The trick is to make sure that PATH is empty before path_helper runs. In my ~/.bash_profile file or ~/.zshrc I have this:
if [ -f /etc/profile ]; then
PATH=""
source /etc/profile