If I need it precise? CNC mill. You know, the same ones the fabs use? Yeah, I just let them figure it out. 
Well, they use routers, which are kinda the same thing in the way that a bulldog is the same thing as a greyhound, but yeah, letting the fab figure out is the best way.
That said, I have use a CNC mill to carve up panels full of prototypes before (IIRC it made sense in terms of price/specs/lead times that I could get at the time and just being a fun experiment). The big problem with using a typical mill in lieu of a purpose-built router is spindle speed. Cutting tools work best at a particular surface speed, which is the linear speed that the cutting edge moves through the material. Small tools at 1-2mm like you typically want for PCB routing, where the cutting edge sweeps a very small circumference need high rotational speeds to get the desired surface speed, so it's not uncommon to see things like PCB routers with 60,000rpm spindles, or sometimes even faster. Cutting tools also have a defined chip load, which is the amount of material removed by each pass of each cutting edge, which sets your feed rate as a function of RPM, so there again small tools with small chip loads need high rotation speeds to cut efficiently.
I was using a Tormach PCNC 1100 with a ~5,000rpm top speed, so performance on a 1.6mm tool was far from optimal, but it got the job done. I threw a chunk of thick acrylic from the scrap rack in the machine, drilled tooling holes and made threaded hold-down holes in the acrylic in place, and milled relief channels in the plastic to clear where the tip of the tool would pass while milling the boards. For the actual milling I used a drill-point carbide burr, which worked pretty well. The drill point allowed it to pierce very effectively, and the burr left a pretty good edge finish despite the non-ideal cutting parameters, maybe just a bit less nice than what you'd get from the fab. The clearance channels in the fixture weren't strictly necessary, but burrs don't clear swarf as effectively as helical tools so some extra space there was helpful, and drill points aren't meant to cut sideways so it would have been kinda gross. The cutting was kind of slow due to the limited spindle speed, but the great thing about CNC machines is that you can press Cycle Start and then walk away from them.
Of course dust control is important, as with any time you cut materials like this. I wouldn't do it on a machine that wasn't fully enclosed or equipped with really good dust collection. I also wouldn't do it on a machine set up for flood coolant unless it had REALLY good filtration, otherwise the fine abrasive particles produced by cutting FR4 are liable to cause increased wear and tear on the machine and cutting tools down the line. Well, really, I wouldn't do it at all because it's just a whole lot easier to have the fab that has the fancy routers with high speed spindles and fancy dust shoes do it, like Tim said in the first place!
