Depends. Some parts of Berlin can be a bit dodgy. I take the U8 regularly Generally it's safe but stations on that line like Kottbuser Tor have a reputation for theft, pick pocketing, robbery, etc. Lots of people desperate enough in that area that you don't want to tempt them too much by being an obvious target.
I use a weather proof backback (Ortlieb). I got it two years ago and it's great. I walk a lot around town with it and the hip belt is great for offloading most of the weight from my shoulders. I can easily walk for a few hours with this thing. I have the 16" macbook pro, which is not exactly light.