I have also been looking for advice on this topic, and while I don't have anywhere close to the kind of money that silvertiger has access to, I am looking at ways to make smart investments that will pay off in the future.
One mistake I have made is to jump in too quick and buy too many domains that are not worth the investment. I certainly have not lost my shirt or anything, but it is still a waste of money. So right now I have stopped buying and I am saving up and learning as much as I can ... I think this is the most important part, learn as much as you can...
If I had the kind of money you have acceess to, I think I would look for some strong keyword domains that have traffic, and the keywords should be high-paying. These domains will cost more, obviously, but I think they are a good investment... Keywords like Mortgage, Insurance, and Credit pay well, and these are the types of keywords that have a great life span, they are not "trendy" they are everyday issues that millons of people face, and the businesses that are in these areas make millions and millions of dollars...
Just my $0.02 ... Good Luck!!