Well, I guess, it depends on your setting, but I think almost any setting offers some more or less obvious candidates to replace the default icons. If you check out the various forums, you'll find several examples. Keith Baker himself even wrote an article about icons in EberronFor example, 13th Age is a great system, but it’s so attached to the Icons and the setting. It would take some work to adapt all into my new campaign.
Theoretically, you could also get rid of the icons completely, although I think, it's too cool a concept to do that. If you go that route, you have to eliminate several of the class talent choices. It has the largest impact on the Chaos Mage, I think, because of their icon spell list. It's probably more work than identifying replacement icons for your setting, but still doable.
I don't think 13th Age is attached to the setting at all, except through its connection to the default icons. The only example I can think of is the Druid's Terrain Caster class talent, which includes 'Koru Behemoths', but that's easily ignored or replaced.