"かれはジョンさんのおじさんです。"
Translation:He is John's uncle.
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さん may be confusing if you think it is the same as Mr., Mrs., Miss., etc. It is rather the word to show respect and caring than politeness. You can use this with professions like pan-ya san パン屋さん(a bakery or a baker) daiku san 大工さん(a carpenter). In Kyoto, some women say o-imo sanおいもさん or o-mame sanおまめさん instead of just imo(potato) or mame(beans), paying respect and caring about good food. Also, some baby words: o-saru sanおさるさん(monkey)、o-uma san おうまさん(horse)。
It could be a level of politeness I'm not aware of, but the more likely case is simply the fact that in Western countries, we commonly use our first name, while in Japan that is reserved for those you know well and instead the family name is used. So a direct translation of ジョンさん to Mr. John sounds strange, while 田中さん is truly Mr. Tanaka and sounds appropriate.
On a sidenote, there are languages (as we do in Greek) where "Mr John" is totally acceptable. It's a middle ground of politeness. Because "Mr(s) Surname" can be way too official/businesslike. For example it's widely used for our friends' and classmates' parents: (e.g. on the phone) "Hello Mr John, is Alex home?"
That's very interesting. There are instances where it's appropriate to use given name + さん for Japanese people as well. Classmates and less formal colleagues might use that form. People who just started dating might use that form. If the room is full of Tanaka-sans, first names might be used to make it easier to address a specific person. It could be used with some extended family members as well.