I bought a spool to try for river float fishing. It does work quite well for that - it floats well, you can see it easily on the surface of the water, and because it does not cling to the water's surface to the same extent as mono, it is easy to mend the line. In windy weather though, it does tend to blow about easily, being very light.
As far as knots are concerned, I use the double palomar lubricated with lip salve, and haven't had any problems so far. I tie a micro swivel to the end of the nanofil, and tie the monofilament hooklength to that.