Well, I don't think I've ever actually removed the language files, but I've heard it widely reported that Adobe software and Microsoft Office have problems with it. Creative Suite, specifically, will insist on being reinstalled.
See the Monolingual FAQ for example.
Part of it is because iTunes tends to include a lot of resources internally that a normal native application wouldn't due to the application's project design for building to Windows as well. iTunes used to be a big Metrowerks PowerPlant-based application and they kept with it for a long time due to the dual target platform nature of it; they've moved on from PowerPlant recently, but as to specifically what the current design/approach is to still make the project easily build-able for Windows, I'm not sure.
A lot of the resources in the application bundle are images and language localizations:
If trimming space is of interest to you, you may want to try running Monolingual on your system:
use monolingual and remove all languages you don't speak from all applications you have. The first time you use that it will clean from 2 to 5 GB of space, depending on how many apps do you have with localization on other languages. This can also be used to remove unwanted CPU architectures from the applications (like PPC support if you just have intel macs).
CleanMyMac will get you a few gigs back. To see exactly which files are taking up the most space, download this and run it. It's called Disk Inventory X, and after a quick analysis, it will tell you where the largest files are, which will help you in deleting the hard drive space hogs. I would probably get a bigger hard drive if I was you, as you don't really want to be deleting operating system data to gain a few megabytes back. Trust Me. On my old MacBook, I figured that rather than paying $80 to get a way bigger hard drive, I would start deleting languages, keyboard layouts, printer drivers and all that stuff from the computer. I got back about a gig of space, and I couldn't print anything from any printer, couldn't remap the keyboard if i wanted, and a bunch of other annoying things. If you really feel like deleting them, have a look here.
For the 1st bullet: http://hints.macworld.com/article.php?story=20010613140025184
2nd Bullet: I'm not too sure, but I'd leave most of it alone if I were you.
3rd: You could do a clean install of the OS from the grey discs that came with your computer.
4th: My /Library/Updates is empty except for a single plist file. What OS are you currently running?
If you're just looking to free up space on your drive, look into Xslimmer. A free alternative is Monolingual which will remove excess language files, but doesn't clean out unnecessary processer code like Xslimmer does.