I will help you with this... or will I help you in this? Now I'm too confused to help...
On a more serious note, oftentimes, I think one preposition simply sounds right, even though others would be acceptable. For example, my kids always say, "This happened to me on accident," which always sounds "off" to me (I'd say, "This happened to me by accident"). However, I've lately noticed a lot of others saying "on accident" as well, so maybe it's a mere matter of preference?
Back to with this vs. in this, I think it can depend on the context. For example, I'd say:
- I will help you with this question. I will help you in this matter.
- I will help you with your homework. I will help you in your time of need.
In each of these examples, I wouldn't want to swap the prepositions. I'm unaware of any hard-and-fast rule dictating when one should be used over the other.