How can I stop applications from preventing restarts? I have some applications that routinely prevent restarts from happening correctly (most often iTerm2 and Slack, though others participate as well). When I request a Restart, these applications will present an "Are you sure?" dialog and halt the restart process.

This annoying most of the time, but especially so when I've requested system updates to install overnight and I instead waste the first several minutes of my day after clicking "Yes I'm sure" and then allowing the reboot to proceed.

Is it possible to tell OSX to always reboot when requested and never stop for user input?
If you insist to not save any work, open terminal and run sudo shutdown -r now

You could force the updates as well before issuing the restart with softwareupdate -ai and never see an “Are you sure?” or “Save this data?” dialog since the shutdown command sends SIGKILL which kills as opposed to asking nicely for programs to exit. 

Back up your files, the filesystem will be safe but your data in specific files won’t necessarily be safe.