[NB: this question is short because it came from Twitter]
This is a timely question because I was just reflecting the other day on my deep desire to read the riot act to potential submitters.
My short answer to your question is:
But that's not very helpful, is it? Fundamentally, in my dream submission-reading life, what I am reading are manuscripts that are ready to be seen. Manuscripts that have been redrafted once or twice. Or non-fiction submissions that contain ideas that have been properly thought through. Or 'young adult novels' that actually consider their readership instead of having main protagonists who are thirty.
Most agents and publishers who read submissions spend a lot of time reading manuscripts that are simply not ready. And the time that we take reading and then rejecting them is time we'd really rather spend on the manuscripts that are ready. Instead, we are always short on time to read our clients' manuscripts and to find new clients.
The best thing that any writer can do for themselves when they're in the submission phase is to make sure that their work is really, truly ready to be sent out. That doesn't mean that it should be perfect. It means that they should make it as good as they, individually, can. Because none of us can ask any more than that. And making it as good as they can means not sending it in with typos everywhere. It means not sending in something that that agency isn't interested in - this is a 'rookie mistake' and it immediately reveals that the writer has not read the submission guidelines, which doesn't predispose the agent/publisher towards the writer.
If what my question-asker really wanted was for me to say what genres I'm looking for, well, that would be telling. What I'm always looking for are great stories for adults and children, and great non-fiction ideas. I can never define exactly what I'm looking for because it's very much a case of knowing it when I see it. Great writing is alchemy. None of us knows which chemicals go into it - we just know that we like the gold at the end.