Safe is a tiny single executable (<1MB) and is very
easy to use compared to TrueCrypt. It doesn't support pagefile encryption or run on a ramdisk on WinXP, although this isn't a big deal since XP is on its way out. The differences between Safe and TrueCrypt are briefly discussed on the Safe-About page here: http://www.getsafe.org/about#download
How is Safe different from TrueCrypt?
In short, Safe is file-based and TrueCrypt is block-based. Neither is strictly better and the pros and cons of both approaches are explained in detail at the EncFS extended introduction page.
In general, if you're wondering why you'd use Safe over TrueCrypt, here is quick summary:
Safe allows you to use your existing EncFS encrypted data on Mac/Windows.
Per-file encryption is much faster on network storage you don't control, like NFS, SMB, Drobo, Space Monkey, Dropbox, Google Drive. Most of their drivers/protocols are file-based. TrueCrypt is block-based, i.e. all data is stored as a single potentially giant file. This affects the performance of algorithms focused on caching and deduplication.
Safe was designed to be much easier than TrueCrypt to use. Try making a new encrypted disk with TrueCrypt, then do the same process with Safe and you'll see what I mean. TrueCrypt is very intimidating to set up for people who don't intimately understand how cryptography works. Safe just chooses the most secure defaults.
Please understand that Safe is not a competitor to TrueCrypt. They are different tools for different situations. Use the right tool depending on the nature of the data you are keeping privte. Safe is another tool in this ecosystem of encyption tools. The main goal is to help more people take control of how their data is stored and transmitted and to hopefully bootstrap mainstream digital privacy awareness.