Can't remember exactly what safestrap does but if I remember right, it does the same as CWM/Rom Manager.
Titanium backs up all your applications and data to those applications. Say you beat Angry Birds, Titanium backup will backup the app and all the progress (data) that goes with it. That way it can be restored into any ROM or phone.
Rom Manager and clockwork do what is called a nandroid backup which is a complete carbon copy of your system. If you restore a nandroid your phone looks exactly the same as it did when you made it.
You use Titanium as basically a migration between phones and roms and you use the nandroid as a backup in case anything goes wrong you can go back in time like nothing happened!
Well said rupik. Safestrap is just a kind of alternate cwm based recovery (that allows for 2 systems). Whatever recovery you use, when u find a rom you like and after its all set up the way you like it...back up all apps/data in titanium. Then make a "nandroid" backup in recovery (regardless of which app you used to get there). You should be set then. I go 1 step farther and use launcherpro just so I can make a backup in that program and keep all my honescreens restoreable.