Your best bet, as many have prescribed here, will be Qt. It works DECENTLY well under GNOME and fantastically under KDE (ofc) if you're concerned about the Linux market, and works pretty well on Windows, too. Personally, with QML and the ability to style applications using stylesheets (not full CSS) and adding scripting support with QtScript is a win-win for me.
However, it really depends probably on the kind of application you're looking to build. If anything (probably silly too), you could build a HTML5 container using Qt, build a API that communicates for native actions and render the rest of the application in HTML5. Better off just making a SaaS, however.
Disclaimer: Hard-core KDE user and FOSS advocate (read: not a freetard)