Main thing is being able to add other musical elements that stays in key with the song you sample. Also, I sometimes find it hard to match textures/tone of sample with keyboard/softsynth sounds, but playing with different instruments, Fx, eq, etc can help get you in the ball park...a little music theory doesn't hurt either for figuring out the key and what fits!

Sometimes just sitting back and dissecting the sample to determine what instruments were used and thinking about how they got them to sound the way they do can help you decide on what to add to fill it up. Sometimes less is more...so adding the right sounds and notes can be more important than how busy it is...

these are just suggestions as I still struggle with this as well...