This discussion is largely for fun. Don't take it too seriously or get angry over it. But it is an interesting comparison.
East vs West
I don't think 50 was ever king of the East, especially since Jay Z and Nas repped the eastside hard.
The Game, however, was probably the biggest mainstream rapper in the west in the 2000's decade as the West side died after the 90's. Game did more for his city, but only because his city was largely empty.
Image
50 Cent in 2003 had nice abs, the women wanted him. Girls, at least all the ones I knew, loved 50 Cent. He took a largely male interest and made women listen to it.
The Game had a more dark grim image about him. He's always been kind of scary looking (but not ugly at all), but he has that hardcore intimidating gangster look that the west needed.
Feud
50 Cent was a huge credit to Game's early success, no lie. But 50 Cent beefs with just about everyone (he's had like over 20 beefs). But the beef between them seems like it's over now. The Game's 300 bars is memorable, and 50 failed to put Game out of business. And in the later part of the decade, Game did much better than 50, who was practically unnoticed domestically from 06-12.
Reputation
50 Cent definitely has more fame. Everyone in the US knows who 50 Cent is, but people have no clue about any of the music 50 put out after Massacre. But internationally, he's making a ton off of what he released earlier in his career. In the US, though I say it's The Game.
Everyone knows who 50 Cent is. All our grandmas have heard of him. But if we're talking about people who are into rap, The Game definitely has been doing much better lately.
Features
Both rely on features to stay relevant, IMO. Major Distribution, come on. But Game uses them as much more of a crutch. While he's excellent at adapting to other people's rap styles, he often limits his own artistic contribution by relying so much on other artists.
Rap Technique
Both lack lyrically. 50 has more multi's but his rhymes are so cliche (bitch/shit/dick) and so repetitive. The Game has practically no multi's in his songs, but his rhyming is a little bit more creative. Neither are great lyricists. Both make up for it with flow and delivery. 50 Cent has a smooth easy-going naturally delivery and flow. Whereas Game often has a cathartic hardcore flow.
Albums
Get Rich will always be 50's most memorable, as Documentary will be for game). I think Get Rich is more listenable, unique and overall better than Documentary.
Self-Destruct, Curtis and Massacre were good, but not great. Doctor's Advocate, LAX, Red Album and Jesus Piece were all solid albums, but none of them will go down as the all-time greats. I prefer a majority of Game's albums though.
So. 50 had 1 classic album and fell off after that. Game seems to be coming close and closer to getting it, but ends up coming short.
Verdict
Both are close to equal in quality IMO.
I'll go with Game, personally. But if you pick 50 Cent, I wont be offended.