It really depends on what you are looking for. I have a GM card that I've had long enough that I get 5% or 10% credit up to $500 per year towards a new GM vehicle. $3,500 came in handy a few months ago when I purchased a new truck (I don't think they offer such a good deal on new GM cards though). Once I hit my $500 in annual earnings I don't use the card anymore.
However, airfare is what I really use points for. Living in Atlanta makes it pretty easy to play the points game. I use an Amex Rewards card that I get between 1x and 5x points on purchases which I then use for airline ticket purchases that usually equate to $0.015 to $0.03 per point. Meaning if I'm looking at a $500 airline ticket and it requires anything more than 35,000 points, I don't use Amex points and pay cash or use Capital One points.
My business card is a Capital One that gives me 2x airline points. I like that but you can't play the points game with this card. If I buy a $2,000 airline ticket it costs me 200,000 points regardless ($100,000 in purchases at 2x). How does this differ from the Amex points I use? I once was able to purchase a $2,000 airline ticket for my wife to South Africa for 75,000 Amex Points. I only had to spend roughly $35,000 to $40,000 in purchases because I'm able to average that with reward points that range from 1x to 5x.
If you want cash back, find the one that has the best cash back option. Travel, store credit, etc., figure out what and where you are going to purchase and do the math like I did above. Also look closely at what teaser deals there are out there. Amex recently offered me 100,000 bonus points to upgrade to a Platinum card but I missed my window

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