Workflow is really good about pausing everything when the service stops and picking right back up when the service restarts.  Things like stopping/starting/restarting the service, or rebooting the server, never really seem to cause issues for Workflows that I have seen.  And upgrading will automatically handle the service stops and starts while the upgrade is in progress.

Personally, I hold production upgrades until after hours to minimize impact to staff-run processes, and then just verify it's running properly again after the install, but I don't think I've had a major issue with Workflow upgrades.

If you are really conerned - make sure you have the installer for the current version you are on, and make a back-up of the Workflow database before the upgrade.  In things go south, you can uninstall Workflow, restore the back up database, and then reinstall the prior version.