Before talking about my experience, I'll just say that I grew up first playing OTB first at a young age, then started playing online. From your question, I also assume you haven't played OTB at a tournament yet.
Online games with long time controls are quite different to OTB. Staring a long time at the screen, on the same position, strain the eyes, and concentration can drop with the temptation to open a new tab during opponent's turn, or start some music. OTB, at most, sitting for a very long time can be uncomfortable, and keeping a straight back is hard once the game has gone on for long. Nevertheless, it's easier to keep concentration OTB than online.
With rapid and blitz games though, the difference is smaller. One key thing in OTB though is the feeling of hitting the clock in zeitnot, which is much more stressing than moving a piece online. Same for casual games, but like it was pointed out, it's easier to set up variants (try 4 man Blitz, it's great :))
The biggest difference between both though is that you're more physically involved OTB. In terms of comfort, you can settle down however you want in front of your computer, but you can't bring more than some food OTB at tournaments. Moreover, you see and touch the piece physically OTB; moving the mouse has a duller sensation because it's been held for a while in the same position. In tournaments, there's also the striking silence rythmed by hit clocks, it's very impressive the first time you experience it.
For all these reasons, I believe there's a big difference between playing online and OTB. Online is more convenient. OTB has a stronger, more unique feeling to it. If you can, try experiencing an OTB tournament for yourself.