On the surface, this seems like it would fix a lot of things. But, what is one subject? How does the budget get done? Is the budget a combination of 500 bills now, or is the budget one subject? If the budget is one subject, what defines a budget item? (Everything has spending attached to it). What about the Farm bill - does E15 gas production qualify as a farm item because it uses corn in the production?
A better way might be to give the president line item veto power. This would allow the bulk of the bill to be passed and send the vetoed parts back to Congress for more work. It would also eliminate the ability for congress to hold up major legislation by putting an objectionable item in a larger bill. Line item veto is common for State Governors and works pretty well. We have a viable pattern to follow with long years of practical use.
I do agree that unrelated items should be kept out of major bills. A bill on hospital reform shouldn't have a line item for military appropriations in it for example. This too can be kept in check by a line item veto.