The major difference (imo) is that your ears dont get tired as fast. This obviously also includes that you dont listen too loud (listening loud will result in weird-sounding mixes anyways because of how ears work.) and take breaks. You lose focus and concentration quicker when using headphones, so I'd use them to check bass + take a reference if youre familiar with the headphones you have. I bought a pair of little Genelecs a few years back, and they roll bass off at 80hz + my room rings at 120-140hz which results in me unable of hearing the 70-80hz at all. When I mix, I do balancing, panning, etcetc on monitors and only switch to headphones (DT770) to check bass and have a reference listen.
Also, if you buy monitors I really suggest buying stands and so getting the freedom to move the speakers away from the wall and to avoid the reflections from your table.
About the soundcard, Ive had good experience with Focusrite stuff, both USB and firewire. If you have enough budget, consider Motu or UA (apollo, the little one).