As this is the European Rail Travel forum, I will of course advise you to take the train.

For checking routing options, I would say bahn.de is your best option. It will even show you a map so you can see where the itinerary goes. For actually booking trains, you generally need to use the website of the appropriate operator - see specific advice below.

I'm actually seeing a daytime option for 13h39 (dep Milan 09:05, change at Verona Porta Nuova and Munich Hbf, and arrive Prague at 22:44).

However, as AdventureAdam says, you can make it more time effective by taking an overnight train - and in that case it probably becomes comparable to flying (in terms of time taken up travelling). And it also saves you a hotel bill. However, I would advise against taking just a seat on the overnight trains - a 6-berth couchette is a lot more comfortable, and normally only €10-€16 more expensive; and a sleeper compartment is even better, if you can afford it.

There are actually (at least) three night-train options:

1) via Zurich: dep Milan Centrale 14:25, arr Zurich HB 18:28, dep Zurich 19:42 arr Praha 10:31. I guess Milan-Zurich can be booked at www.sbb.ch and Zurich-Prague can be booked at bahn.de (A 1hr14 connection in Zurich should be sufficient, and they'd probably hold the night-train a bit if necessary (if they knew your train from Milan was running late) but to play it safe, you could leave Milan on an earlier train...)

2) via Munich: dep Milan Centrale 21:35, arr Munich Hbf 06:30; then either dep Munich 07:13 on the ICE, arr Nuremberg Hbf 08:31, dep Nuremberg 08:42 on the IC bus and arr Prague 12:19. However, personally I would avoid the IC bus, and dep Munich Hbf 09:01 on the direct train to Prague, arr 14:44 (a bit slower, but a lot more pleasant, and possibly cheaper...) First option can all be booked at bahn.de; for the second option Milan-Munich can be booked at bahn.de and Munich-Prague at cd.cz. See Seat61's Munich-Prague page for money saving tips.

3) via Vienna: dep Milan Centrale 21:35, arr Vienna Meidling 08:33, dep Vienna Meidling 09:31, arrive Praha 14:21. Should be possible to book both parts at www.oebb.at

For scenery, the option via Zurich is probably best, as it takes you through the Alps. If price is your main factor, then you'd have to compare all 3 options to see which is cheapest on the day you want to travel.

Of course, for each option you could lengthen out your trip (ie: leave Milan earlier for option 1, depart Munich/Vienna later for options 2 and 3) in order to have a stopover in the relevant city - they're all well worth a visit. And, unlike airports, the station is the city centre in each case (well, I think Meidling is a bit out of a town, but still a lot closer than the airport...)