If you don't need to support IE8 (which is at 1.38% global market share according to CanIUse), then cross-browser differences just aren't the problem they were in the 1995-2010 era. The event model, DOM querying, classList, CSS animations & transitions, fast GPU rendering via CSS translations, box sizing, history management, localStorage, ES5, JSON parsing, geolocation, websockets, all of these are well-supported by standardized native APIs on all major browsers.

http://caniuse.com/#search=event

http://caniuse.com/#search=querySelector

http://caniuse.com/#feat=classlist

http://caniuse.com/#search=animation

http://caniuse.com/#search=transform

http://caniuse.com/#feat=css3-boxsizing

http://caniuse.com/#search=history

http://caniuse.com/#feat=namevalue-storage

http://caniuse.com/#search=es5

http://caniuse.com/#feat=json

http://caniuse.com/#feat=geolocation

http://caniuse.com/#feat=websockets

Even things like the template tag have reasonable support. It's only when you get into bleeding-edge stuff like webcomponents and web animations that browser support starts to drop off, and unless you're using Polymer (which polyfills all that), that's unlikely to matter.

You deal with them one at a time. It's not like there's magic involved.

Our SPA isn't even using jQuery. Loadtimes are fast, app is very fluid.

Many people seem to not understand that when you query the dom for a node, you can store that node and reuse it throughout your app.