Principal Rhine city, not unknown (4)
I believe the answer is:
main
'principal' is the definition.
(both can mean major)
'rhine city not unknown' is the wordplay.
'rhine city' becomes 'Mainz' (city on the Rhine).
'not' indicates named letters should be taken away.
'unknown' becomes 'z' (algebra).
'mainz' with 'z' taken away is 'MAIN'.
(Other definitions for main that I've seen before include "Ocean or principal pipe" , "Most important - high seas?" , "Source of water" , "Chief; sea; pipe" , "Chief in importance" .)