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Sometimes you face some browser compatibility issues, when you use custom fonts and icons since each browser reads a certain extension of fonts and normally they render font icons somehow in a different way specially if you are using Fontello on the other side border-radius has some issues if you really specify the radius corner, it won't be handled on all IE & Safari versions, the Flex-box issue as well, it's not compatible with many browsers so sometimes you need to make some Javascript code in order to replace it with some CSS.
Sure , Fixing common browser compatibility issues can be frustrating.But usually every issue has easy solution if you know where to look.So pick your favorite cross-browser testing solution and go to work :).
Browser compatibility should not be a problem if you go with Twitter Bootstrap (getbootstrap.com). Go with it and you will be happy inshaAllah :)