Yes, they acquire cruft after a bit of time. In the Mac world, this typically means that an application leaves something unobtrusive in the System Folder that is difficult to detect.
An extreme, non-Mac example: the university where I worked had 170 (lousy) PCs in a user area. On a weekly basis, three or four were returned for re-imaging of Windows XP, which was a much greater proportion than on other more standard PCs. So I conducted an experiment. I configured one PC to boot, logon as a domain user, launch some applications, reboot and repeat. For a month. After that time, free disk space had fallen from 20GB to 20MB, and the OS itself used more RAM (not a huge figure more). Boot up times over that period degraded by 50%. When free disk space hit 20MB, I ran it for another week, expecting the PC to fall over. However, it continued to run, suggesting that XP has some sort of scavenging mechanism in such circumstances.