For a singer, all the difference. Certain keys bring out specific frequencies in the voice.

For guitar players who are folkies, open-string keys make the difference unless
capos are used.

Some synesthetic people associate keys with colors. They make a visual distinction.
Many were well-known composers.

For some instruments, such as brass, flat keys are generally preferred (concert, not
transposed) and for strings, sharp keys. Depending on the range of the instrument
plus its frequency response, the key does affect this.

Frank Hamilton