Personally, I have gotten the best results from doing hills as my speed work. A good 1/4 mile hill at a 4-6% grade will do wonders for your lungs and legs.

Example of results: March of 2004 I ran a 43 mile ultra that is a combination of gravel, hills, and long flat stretches. Unfortunately the 12 miles of hills come at the end of the race. Finish time 08:01:23. So for the following year I did A LOT of hill training. All weekly runs were done on the same 2 mile loop of rolling hills. After a while though (3-4 months) my HR would not change much going up and down the hills. As a result My legs and lungs became a lot stronger and running on flat ground became easier and I recovered from steeper hills faster. Finish time for 2005, 07:19:45. I've always said hills are speed training in disguise.