Yes this is totally possible in French, much as it is in English.
Who are your best friends ?
would translate to
Qui sont vos meilleurs amis ?
A singular question could be
Who is here ?
Translating to
Qui est là ?
For the party example, the translation is more complicated.
Who is coming to the party ?
would actually translate to
Qui est-ce qui vient à la fête ?
Because in French logic, one must say "Who is it who is coming"
The reason for singular or plural is the same in English and in French. When one knows that the subject is plural, one uses the plural form. Otherwise, when in doubt, one uses the singular form. For "Who is coming to the party ?", the [group of 0 or more people] coming to the party could possibly be singular. So the sentence uses singular.