I think most people want what's best for humans at least, so it's reasonable to start from humanism and move forward from there. Personally though? I think the well-being of all conscious beings is important, so I try to maximize the best possible benefit for everyone and diminish the possibility for suffering whenever I can.
I understand that people don't think you can derive an ought from an is; that is, that none of the facts of reality provide a direct answer to what's right and wrong. But ultimately I think those people are just arguing semantics and missing the point that we generally have a good idea of what state other people and animals prefer to be in and in my opinion you have to justify any action that would prevent those preferred states.
If anyone honestly believes that meaningless suffering is moral and general well-being is immoral, I'm not really interested in their arguments except to satisfy my curiosity for how they've gone so far off the rails. Still, I can understand why certain people don't take morality seriously since the answer isn't always obvious unless you subscribe to some magically endowed absolute morality. Simply opting out when you can see no clear right or wrong makes sense- I'm just not willing to go that way, personally. I would rather try to make the world a little better than sit idly by because I'm not sure if it really matters. If some cosmic force decides that's wrong, fuck 'em.