What do you want to see? And where do you want to end up?
Last month I went from Pattaya through Isaan to Mekong, along Mekong and up to Chiang Rai and Chiang Mai.
First stop was Lalu in Sa Kao to see the earth formations. Photos at this site, almost at the end:
http://khunkurt.wordpress.com/2012/02/05/road-trip-sa-kaeo
Google Maps:
https://maps.google.com/maps?q=14.051497,+102.575651+(Lalu)
The last part of the road is a dirt road. The earth formations are wide spread, continue driving to see more of them. But be aware that you have to take the same way back, even though Google will say that there is another way out (north of the lake Huai Yang). I had to give up on that, it is a single track dirt road, that you need an off roader to manage, if possible at all.
Next stop for me was in Buriram to see some old ruins. Phanom Rung National Park have ruins similar to Angkor Wat, but much smaller. There are two entrances, if you do not have trouble climbing stairs take the lower one as you will get a very nice view to the main building.
Google Maps:
https://maps.google.com/maps?q=14.532500,+102.945278+(Phanom+Rung)
There are some more ruins near by, at Prasat Muang Tam, you will actually pass those first on your way. If you only want to see one set of ruins, skip those and go directly to Phanom Rung.
Google Maps:
https://maps.google.com/maps?q=14.495787,+102.981652+(Prasat+Muang+Tam)
I then went to Sisaket to visit the temple Wat Pa Maha Chedi Kaeo, better knows as Wat Lan Kuad - temple of a million bottles. A few photos at my website, although you probably cannot read the text (in Danish):
http://rejse-til-thailand.dk/tempel-af-flasker
Google Maps:
https://maps.google.com/maps?q=14.618141,+104.419260+(Wat+Lan+Kuad)
From there I went up through Isaan to Nong Khai, I didn't see anything interesting on the way, a rather boring drive, except for the usual excitement when ramming down the pot holes - I am driving a scooter so I feel those more than on a big bike.