As Howard said, going into maintenance mode is the safest thing to do.
I will provide my own 2 cents ($US). I run my own small Moodle. Right now, four courses running with a total of around 160 students. My moodle has around 8 add-ins. Nope, I don't put my Moodle into maintenance mode when updating everything.
Here's what I do. In a temporary folder, I prepare my new (upgrade) Moodle with all these add-in, and with a copy of config.php. Then, I wait for a time when I see no students have done anything for 5 minutes (i.e., no online users.) Often, early morning before 7AM is a good time. Then, through SSH scripts, I rename my current moodle, move my prepared new moodle into the right
server location, and quickly do the update. For my small Moodle (moodledata = 5GB,
sql = 1.5GB) this update takes less than 3 minutes. Oh, I had already tested the new Moodle in a local
MAMP environment, making sure everything new was working. So, there is a very small window (< 3 minutes) where a student might try to do something during my update. I take this risk, and so far have never had a problem (after doing my updates this way for nearly 8 years.)
Others here on Moodle.org will explain their methods.
Yes, I really don't have any problem putting Moodle into Maintenance mode, but doing so might take me, oh, 2-3 minutes, so there is not much difference. In my own instructions that I sometimes pass along to others, yep, I say "put Moodle into Maintenance mode." Sometimes I don't practice what I preach!