I almost agree with others who say U2 are simply too old to achieve mainstream popularity again, but not quite.
The thing is, since vertigo, they just haven't created a hit of that caliber, as strong as Beautiful Day or whatever else before it.
Now, I recognise this is entirely subjective, and others might disagree, but I just think that - although they've made some really beautiful music with NLOTH and SoI - they've failed to successfully yield a single with that 'spark', a proper hook that makes the song soar... that indescribable 'it' that just makes a song catchy, feel-good, and makes people want to turn up the radio, or sing along at a gig.
The last singles to do that were back in 2004, and I simply believe they haven't created a single that strong since then. That's why I think they've failed to be 'relevant' lately. In terms of making the next Beautiful Day, One, or WOWY.. they just haven't. GoYB didn't have it. Invisible didn't, as cool a song as it was. I feel The Miracle almost had it, but not quite.
So, with that in mind, until they offer a lead single that's as 'hit-worthy' as Beautiful Day, I don't think I can attribute their failings simply to their age; they need to make stronger singles if they want hits. I think if they do that, they still have a shot at success.
(Of course, I know music being 'good enough' is entirely subjective and not really quantifiable; but I for one think they can simply do better if they want a hit single.)