Major Components - Make sure the major components in the home are good: roof, HVAC, electrical, plumbing and foundation.
Minor Plumbing Issues - Most fixer uppers have minor plumbing issues, especially if it has been vacant. This is normal.
Solid Layout - Make sure the home has a good layout. Removing a wall or widening something is one thing, but if the whole layout of the house will need an overhaul, you make be talking about a lot of money to make that happen.
Health Concerns - With a vacant or older home, there can be all sorts of issues that can be very costly to deal with such as: pest infestation, mold, radon, asbestos and lead. Getting rid of any of this (and some other issues) can take up a big chunk of your budget. Make sure you check those things out before you purchase as well.