If we need to query a table based on some set of values for a given column, we can simply use the IN clause.
But if query need to be performed based on multiple col
Ensure you have an index on your firstname and lastname columns and go with 1. This really won't have much of a performance impact at all.
EDIT: After @Dems comment regarding spamming the plan cache ,a better solution might be to create a computed column on the existing table (or a separate view) which contained a concatenated Firstname + Lastname value, thus allowing you to execute a query such as
SELECT City
FROM User
WHERE Fullname in (@fullnames)
where @fullnames looks a bit like "'JonDoe', 'JaneDoe'" etc