General types of applications

Anti-virus apps are notorious for slowing backups to a crawl, or hanging them entirely. 

1. Many experienced Mac users don't run any such apps at all. If you do use one, at a minimum exclude your Time Machine drive from them (some can actually corrupt your backups!)  For the gory details about viruses and other malware, see Thomas Reed's Mac Virus Guide and/or this User Tip by frequent poster Klaus1.
   

Virtualization apps, such as VMware, Parallels, etc.

1. In many cases, the virtualized OS is stored in one or a few very large OSX files.  Any change, no matter how tiny, means the whole file is changed, and will be backed-up the next time.  That can use a lot of backup space very quickly. One solution is to just use a much larger Time Machine drive;  another is to exclude the files from Time Machine backups, and back them up separately with another app, such as CarbonCopyCloner or SuperDuper, to a separate partition on the Time Machine drive, or a different drive.  See the green box in Time Machine FAQ #27 for links and some additional apps.
   

Databases, P2P, and Torrent apps that store their data in a database (or large file). 

1. Any change, no matter how tiny, means the whole file or database is marked as changed, and will be backed-up the next time.   Some 3rd-party Mail apps work this way, too.
   

Other Backup apps (especially online apps such as Mozy or Carbonite). 

1. Some of these put files on your system, to keep track of what's been and/or needs to be backed-up.  Sometimes these get fairly large, and are updated very frequently, so unless you exclude them from Time Machine, they'll take a lot of space in your TM backups.   These files may be hidden, so check with the maker to locate them.  If you use CrashPlan or DropBox, see below.
   

Software included with external disks

1. Some versions of software supplied by disk makers may not be compatible with the latest version of OSX, and/or may interfere with Time Machine.  WD SmartWare, for example, can prevent Time Machine from accessing network backups.

Some specific applications

This is not an exhaustive list, but a few that have been reported several times.  Some may apply only in limited cases -- different versions of an app may be fine on one version of OSX but not another.   Thus, if you have an app listed here, the problem may only apply to some versions.

Aperture if it is open during a Time Machine backup, the entire Aperture library may be

1. backed-up, not just the changes since the previous backup.
   

Calendar (iCal prior to Lion).  If your calendars are being synched over the internet, look

1. for thousands of temporary files in ~/Library/Calendars/Calendar Sync Changes.
   

CrashPlan keeps some files in the top-level /Library/Application Support/CrashPlan folder.

1. You may want to exclude the entire folder, or just the files that are large and/or updated frequently, from Time Machine backups.
   

Deskovery has been reported to cause momentary system freezes during backups.

DropBox has some files in a hidden folder in <your home folder>/.dropbox

1. You may want to exclude the entire folder, or just the files that are large and/or updated frequently, from Time Machine backups.  Since the folder is hidden (the leading dot in its name), you'll need to check the Show invisible items box on the exclusions window.
   

Entourage (an e-mail app) uses a database for its files.  See Databases in the blue box.

FileMaker and FileMaker Pro databases can be corrupted if opened while being backed-up,

1. so should be excluded.  See FileMaker and Time Machine.
   

Finale has a plug-in for the 2012 version that can cause Time Machine to hang or crash.

1. Delete the following file:  /Library/Spotlight/Finale.mdimporter  That means some of the specific information in the files won't be available for Spotlight searches.
   

GoogleDrive is reported to cause Finder crashes after doing a full restore from Time Machine.

Microsoft Word can't save files (either manually or via Word's autosave) if a TM backup is running (or, some say, just turned ON but not running a backup).  Some report they can turn the autosave off and use the "Make a backup copy" option instead.  This problem may apply to Lion and Mountain Lion only.

Parallels see Virtualization apps in the blue box.

Tech Tool Pro if you use the Directory Protection feature, exclude your Time Machine

1. volume from it.  It can slow your backups down significantly, and it won’t help fix a problem there, anyway.  In addition, you probably want to exclude its files (in the top-level /Library/Application Support/Techtool Protection folder) from Time Machine backups, as they may cause large backups.
   

Thunderbird (mail app) uses a database for its files.  See Databases in the blue box.

VMware Fusion see Virtualization apps in the blue box.

WD SmartWare (comes with some Western Digital external HDs) can prevent Time Machine from accessing network backups.

Disk Images

If you keep much data in disk images, that can cause extra-large backups, depending on the Image Format (type) of disk image and how you use it.

One common use of disk images is detailed in Apple's iPhoto: Sharing libraries among multiple users article.

If you use a read/write disk image or sparse disk image, any change to any of the contents marks the disk image as changed, so the whole thing is backed-up.  On a large disk image, of course, that can take a lot of time and space on your backup drive.

If you use a sparse bundle disk image, however, it's quite different.  When you create one, the size you specify is a maximum size;  the actual size is only the size of the contents.  These consist of a whole lot of 8 MB "band" files;  your data is spread over them.  When files are added or changed, only the added or changed bands are backed-up, not the whole disk image.  

There's another oddity about sparse bundle disk images -- they don't automatically shrink when you delete things.  The vacated space is just marked as available, and will be used for new files first, before new bands are created.  That's not a problem, unless you delete a large amount of data, and wonder why your disk image didn't get smaller.  There is a way to manually "compact" one if necessary.  It's spelled-out in the pink box of Time Machine FAQ #12.