Your first major difference is in the body styles. While they look similar, the MH-250 is an "arch top" style where the body raises up in the middle while the M-400 is a flat top. Myself, I do not like arch top guitars..the edge of the body tends to dig into my forearm and leaves a sore spot after awhile. While it's flat, the M-400 does have a bevel where your forearm should go and I find them very comfortable to play.

According to my ESP catalog, the M-400 is made of alder and not mahogany. There is a BIG difference in body woods. Agathis is a lower-end wood and has a lesser tone response. Alder is a balanced wood lending to somewhat balanced tones.

Your biggest difference in the two is the pickups. The MH-250 uses ESP pickups designed by EMG. While the name EMG can excite you they may not be what you think they are. Jackson uses alot of Duncan Designed pups in their gits but while they're made to Duncan's specs, they are NOT Duncan pups and the tone is proof. The M-400 uses EMG active pickups, and here's where everything changes. Active pickups use a battery to supply power and while some people don't like this, tone-wise they are hard to beat. They're bright and have an excellent overall response.

The neck shapes have a large impact, too. The M-250 has a "thin U" shape while the M-400 is "Extra thin." This means that by rights the M-400 should be much easier to play.

I can tell you alot of other things but in the end what you have to do is try them both and decide which one YOU like the best.