Second game takes forever to load and then crashes.

I am currently trying out multiboxing for the first time. I am playing Diablo 3. The first game launches with no problem. However, when I launch my second game it takes over 5 minutes to load and then when I am finally able to get in game I try to start a run with 2 accounts and the second always freezes and then crashes. Any ideas on what I am doing wrong here?

[lax]

The first game launches with no problem. However, when I launch my second game it takes over 5 minutes to load

If you describe the launch process as "I launch my second game", then this is the problem. You MUST let ISBoxer launch the second instance. What is probably happening is the second instance is attempting to use the same copy of the cache as the first copy (because it's not being launched by ISBoxer), and fails, and the game will not run in this way.

You should have exactly one Character Set, with both of your Diablo 3 Characters in it, and you should be selecting your team from the Inner Space menu (under ISBoxer Character Sets) as opposed to a Diablo 3 Game Profile (which will not use ISBoxer when launching).

Maybe you also want to share your computer specs with us?
Recently i have changed my video card and man let me tell you how better experience i have with D3. After 1.0.5 patch my system was lagging like hell so i change my video card and now doing 4WD multiboxing with Acid rain Spam and bear without any lag on all four instances.
At times i do get one of my instance freeze but in main window i see all WD moving, so i just restart again and it always work for me.