Reducing Lion OS Footprint by removing unnecessary files/folders
We get a lot of questions about this topic here. You can search for earlier similar questions and answers.

Backup first

Make a full backup of everything, a complete disk image, before you go on a spree to delete resources from your Mac.

Deleting More Unused Human Language Resources

Monolingual, which is free, can delete unwanted language support files in the /System/Library/ and /Library/ folders itself, whereas XSlimmer (which I also use) is only set up to delete language support files in the Applications folder.

iPhoto

You can "thin out" iPhoto by removing its voluminous printing templates, but if you delete them, you won't be able to print anything from iPhoto at all.

Right-click on iPhoto in /Applications/iPhoto/ and select "Show Package Contents". You'll discover several hundreds of megabytes of files in /iPhoto/Contents/Resources/Themes/. You can actually delete these (authentication required) but it will change the behavior of the iPhoto app.

Speech synthesis voices

Removing system support files from the /System/Library/ folder is dangerous. The only files I know of that you can safely delete are the speech synthesis voices in /System/Library/Speech/Voices/. You should leave one voice in there should you ever need that feature.

Fonts

You can save several dozen megabytes by deleting certain Asian fonts if you don't need them. Don't delete system fonts directly in the Finder. Rather, do it through the Apple Font Book application, which will prevent you from deleting the "reserved" system fonts that Mac OS X expects to see when it boots up, but permit you to delete "non-essential" fonts.

Screen savers and desktop pictures

Screen savers are in /System/Library/Screen Savers/.

/Library/Desktop Pictures/ has a couple of hundreds of megabytes of files you don't need.

Dictionaries

Mac OS X has a Japanese dictionary and thesaurus, several hundred megabytes in size,  in /Library/Dictionaries/. You can safely delete these if you will never need them.

GarageBand and iDVD files

If you do not use GarageBand or the older iLife program iDVD, you can save many tens of gigabytes by deleting their applications but especially their support files in the /Library/ directory.

With regard to GarageBand, depending on your installation, several gigabytes of data can be removed from two places:

/Library/Application Support/GarageBand/

/Library/Audio/Apple Loops/Apple/Apple Loops for GarageBand/


Printer drivers

Depending on your installation, you may have several gigabytes of printer drivers for printers that you have never actually used. If you are willing to take the trouble, you can delete everything in /Library/Printers/. The next time you turn on one of your printers and try to print to it, Mac OS X Lion will prompt you to download and install the driver needed for that printer alone.

Utilities to help you find files to delete

There are several utilities to list all the files on your hard drive and sort them by file size in various types of charts and graphs. These include: OmniDiskSweeper, which is free; WhatSize, a commercial app; and DaisyDisk. All these are useful not only for looking at system files but also for examining your Documents and user data. You'll find old files that you don't need and can archive or delete, saving further disk space.

Just remember

Just remember that if you do not know what you are doing, you might damage your system and then the only remedy would be to do a complete re-installation of your OS, which would put you right back where you started.