Usually I use Placidus, but there are exceptions.
1. A high-latitude birth can give you very skewed houses at certain times of year. This is really problematic for people born in Scandinavia, the Baltic states, Russian, Alaska, northern Canada, and even Scotland. In such cases I will often look at a range of house systems for the person, notable equal house and whole signs to see if it makes a difference. Then I kind of interpolate. I would also place much less emphasis on houses than on aspects and signs. I'll post an example below of a Finnish prime-minister.
We still have a problem even with equal house or whole signs, however, because you can wind up with the MC in the 12th house!
2. If a birth time isn't known exactly, I would probably use whole signs, because degrees on house cusps are going to be meaningless. You would still need to fasten the ascendant and MC within particular signs. But if someone says, "I was born around 1:30" and can't narrow it further, yet 1:30 puts the ascendant firmly in the middle of a sign, then whole signs make sense. You still need to treat the ascendant and MC degrees with caution.
3. If I want to spend time with a chart, I would probably look at several house systems. Particularly for "cuspy" planets, you can get a better read on whether they stay in the same house, or move around. If it's the latter, I would treat their house position with circumspection. If they stay in the same house, you've probably got something solid.
4. To me, quadrant house systems are far more natural than whole signs, yet whole signs can give a whole lot of supplementary information. I think of Placidus as giving a frontal portrait of the person, yet whole signs (or some other system) as analogous to a profile or oblique picture. Both show a "true" picture of the person, but from a different perspective.